{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T21:56:41Z","timestamp":1793138201223,"version":"4.5.0"},"reference-count":200,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,1,9]],"date-time":"2025-01-09T00:00:00Z","timestamp":1736380800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>It has been known since the early days of the discovery of aflatoxin B1 (AFB1) that there were large species differences in susceptibility to AFB1. It was also evident early on that AFB1 itself was not toxic but required bioactivation to a reactive form. Over the past 60 years there have been thousands of studies to delineate the role of ~10 specific biotransformation pathways of AFB1, both phase I (oxidation, reduction) and phase II (hydrolysis, conjugation, secondary oxidations, and reductions of phase I metabolites). This review provides a historical context and substantive analysis of each of these pathways as contributors to species differences in AFB1 hepatoxicity and carcinogenicity. Since the discovery of AFB1 as the toxic contaminant in groundnut meal that led to Turkey X diseases in 1960, there have been over 15,000 publications related to aflatoxins, of which nearly 8000 have addressed the significance of biotransformation (metabolism, in the older literature) of AFB1. While it is impossible to give justice to all of these studies, this review provides a historical perspective on the major discoveries related to species differences in the biotransformation of AFB1 and sets the stage for discussion of other papers in this Special Issue of the important role that AFB1 metabolites have played as biomarkers of exposure and effect in thousands of human studies on the toxic effects of aflatoxins. Dr. John Groopman has played a leading role in every step of the way\u2014from initial laboratory studies on specific AFB1 metabolites to the application of molecular biomarkers in epidemiological studies associating dietary AFB1 exposure with liver cancer, and the design and conduct of chemoprevention clinical trials to reduce cancer risk from unavoidable aflatoxin exposures by alteration of specific AFB1 biotransformation pathways. This article is written in honor of Dr. Groopman\u2019s many contributions in this area.<\/jats:p>","DOI":"10.3390\/toxins17010030","type":"journal-article","created":{"date-parts":[[2025,1,9]],"date-time":"2025-01-09T05:17:08Z","timestamp":1736399828000},"page":"30","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Species Differences in the Biotransformation of Aflatoxin B1: Primary Determinants of Relative Carcinogenic Potency in Different Animal Species"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3121-1380","authenticated-orcid":false,"given":"David L.","family":"Eaton","sequence":"first","affiliation":[{"name":"Department of Environmental and Occupational Health Sciences, School of Public Health, University of Washington, Seattle, WA 98195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David E.","family":"Williams","sequence":"additional","affiliation":[{"name":"Environmental and Molecular Toxicology, College of Agricultural Sciences, Oregon State University, Corvalis, OR 97331, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger A.","family":"Coulombe","sequence":"additional","affiliation":[{"name":"Graduate Toxicology Program, Department of Veterinary Sciences, Utah State University, Logan, UT 84322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,9]]},"reference":[{"key":"ref_1","first-page":"561","article-title":"Aflatoxin structure and hepatocarcinogenicity in rainbow trout (Salmo gairdneri)","volume":"46","author":"Ayres","year":"1971","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_2","first-page":"960","article-title":"Promotion of aflatoxin-induced hepatoma growth in trout by methyl malvalate and sterculate","volume":"31","author":"Lee","year":"1971","journal-title":"Cancer Res."},{"key":"ref_3","first-page":"2370","article-title":"Dose-response characteristics of aflatoxin B1 carcinogenesis in the rat","volume":"27","author":"Wogan","year":"1967","journal-title":"Cancer Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1016\/0015-6264(74)90239-9","article-title":"Carcinogenic effects of low dietary levels of aflatoxin B1 in rats","volume":"12","author":"Wogan","year":"1974","journal-title":"Food Cosmet. Toxicol."},{"key":"ref_5","first-page":"1649","article-title":"Species comparison of in vitro metabolism of aflatoxin B1","volume":"37","author":"Roebuck","year":"1977","journal-title":"Cancer Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3179","DOI":"10.1007\/s00204-023-03607-z","article-title":"Comparative metabolism of aflatoxin B(1) in mouse, rat and human primary hepatocytes using HPLC-MS\/MS","volume":"97","author":"Gerdemann","year":"2023","journal-title":"Arch. Toxicol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1080\/15376516.2021.2021339","article-title":"Aflatoxin B1: Metabolism, toxicology, and its involvement in oxidative stress and cancer development","volume":"32","author":"Cao","year":"2022","journal-title":"Toxicol. Mech. Methods"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Pickova, D., Ostry, V., Toman, J., and Malir, F. (2021). Aflatoxins: History, significant milestones, recent data on their toxicity and ways to mitigation. Toxins, 13.","DOI":"10.3390\/toxins13060399"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.fct.2018.11.047","article-title":"Aflatoxin B1: A review on metabolism, toxicity, occurrence in food, occupational exposure, and detoxification methods","volume":"124","author":"Rushing","year":"2019","journal-title":"Food Chem. Toxicol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1080\/19440049.2011.563370","article-title":"Present and future directions of translational research on aflatoxin and hepatocellular carcinoma. A review","volume":"29","author":"Wogan","year":"2012","journal-title":"Food Addit. Contam. Part A Chem. Anal. Control. Expo. Risk Assess."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"S28","DOI":"10.1093\/toxsci\/kfq283","article-title":"Aflatoxin: A 50-year odyssey of mechanistic and translational toxicology","volume":"120","author":"Kensler","year":"2011","journal-title":"Toxicol. Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/S0027-5107(97)00289-3","article-title":"Activation and detoxication of aflatoxin B1","volume":"402","author":"Guengerich","year":"1998","journal-title":"Mutat. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1146\/annurev.pa.34.040194.001031","article-title":"Mechanisms of aflatoxin carcinogenesis","volume":"34","author":"Eaton","year":"1994","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_14","unstructured":"Eaton, D.L., and Groopman, J.D. (1994). The Toxicology of Aflatoxins: Human Health, Veterinary, and Agricultural Significance, Academic Press."},{"key":"ref_15","unstructured":"IARC (1993). Some Naturally Occurring Substances: Food Items and Constituents, Heterocyclic Aromatic Amines and Mycotoxins, IARC Press."},{"key":"ref_16","first-page":"615","article-title":"Species susceptibility to aflatoxin B1 carcinogenesis: Comparative kinetics of microsomal biotransformation","volume":"50","author":"Ramsdell","year":"1990","journal-title":"Cancer Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"6492","DOI":"10.1073\/pnas.82.19.6492","article-title":"Aflatoxin metabolism in humans: Detection of metabolites and nucleic acid adducts in urine by affinity chromatography","volume":"82","author":"Groopman","year":"1985","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1021\/tx00044a006","article-title":"Oxidation of aflatoxin B1 by bacterial recombinant human cytochrome P450 enzymes","volume":"8","author":"Ueng","year":"1995","journal-title":"Chem. Res. Toxicol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1093\/carcin\/2.12.1371","article-title":"Interaction of aflatoxin B2 with rat liver DNA and histones in vivo","volume":"2","author":"Groopman","year":"1981","journal-title":"Carcinogenesis"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1080\/00498250500137427","article-title":"Influence of Matrigel-overlay on constitutive and inducible expression of nine genes encoding drug-metabolizing enzymes in primary human hepatocytes","volume":"35","author":"Stapleton","year":"2005","journal-title":"Xenobiotica"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1093\/toxsci\/kfp206","article-title":"Modulation of aflatoxin B1-mediated genotoxicity in primary cultures of human hepatocytes by diindolylmethane, curcumin, and xanthohumols","volume":"112","author":"Stapleton","year":"2009","journal-title":"Toxicol. Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"4790","DOI":"10.1073\/pnas.87.12.4790","article-title":"Five of 12 forms of vaccinia virus-expressed human hepatic cytochrome P450 metabolically activate aflatoxin B1","volume":"87","author":"Aoyama","year":"1990","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1006\/taap.1996.0326","article-title":"The kinetics of aflatoxin B1 oxidation by human cDNA-expressed and human liver microsomal cytochromes P450 1A2 and 3A4","volume":"141","author":"Gallagher","year":"1996","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1021\/tx050358e","article-title":"Dominant contribution of P450 3A4 to the hepatic carcinogenic activation of aflatoxin B1","volume":"19","author":"Kamdem","year":"2006","journal-title":"Chem. Res. Toxicol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1697","DOI":"10.1007\/s00204-013-1108-3","article-title":"Cytochrome P450 2A13 is an efficient enzyme in metabolic activation of aflatoxin G1 in human bronchial epithelial cells","volume":"87","author":"Zhang","year":"2013","journal-title":"Arch. Toxicol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/0165-7992(89)90068-7","article-title":"Mutagenic activation of aflatoxin B1 by P-450 HFLa in human fetal livers","volume":"227","author":"Kitada","year":"1989","journal-title":"Mutat. Res."},{"key":"ref_27","first-page":"2641","article-title":"Metabolic activation of aflatoxin B1 and 2-amino-3-methylimidazo[4,5-f]-quinoline by human adult and fetal livers","volume":"50","author":"Kitada","year":"1990","journal-title":"Cancer Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.3109\/14767058.2014.951625","article-title":"Overlapping between CYP3A4 and CYP3A7 expression in the fetal human liver during development","volume":"28","author":"Fanni","year":"2015","journal-title":"J. Matern.-Fetal Neonatal Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1602","DOI":"10.1016\/0140-6736(91)93295-K","article-title":"In-utero exposure to aflatoxin in west Africa","volume":"337","author":"Wild","year":"1991","journal-title":"Lancet"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"12536","DOI":"10.1021\/bi980895g","article-title":"Structure-function relationships of human liver cytochromes P450 3A: Aflatoxin B1 metabolism as a probe","volume":"37","author":"Wang","year":"1998","journal-title":"Biochemistry"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1358\/mf.2005.27.8.928310","article-title":"Cytochrome P450 3A: Genetic polymorphisms and inter-ethnic differences","volume":"27","author":"Krishna","year":"2005","journal-title":"Methods Find. Exp. Clin. Pharmacol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"6121","DOI":"10.1073\/pnas.94.12.6121","article-title":"Reaction of aflatoxin B1 exo-8,9-epoxide with DNA: Kinetic analysis of covalent binding and DNA-induced hydrolysis","volume":"94","author":"Johnson","year":"1997","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_33","first-page":"557","article-title":"Involvement of cytochrome P450, glutathione S-transferase, and epoxide hydrolase in the metabolism of aflatoxin B1 and relevance to risk of human liver cancer","volume":"104","author":"Guengerich","year":"1996","journal-title":"Environ. Health Perspect."},{"key":"ref_34","first-page":"642","article-title":"Autoactivation and activation of the cytochrome P450s","volume":"36","author":"Ekins","year":"1998","journal-title":"Int. J. Clin. Pharmacol. Ther."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/j.abb.2004.09.010","article-title":"Modelling atypical CYP3A4 kinetics: Principles and pragmatism","volume":"433","author":"Houston","year":"2005","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_36","first-page":"1644","article-title":"Multisite kinetic models for CYP3A4: Simultaneous activation and inhibition of diazepam and testosterone metabolism","volume":"29","author":"Kenworthy","year":"2001","journal-title":"Drug Metab. Dispos."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1021\/bi5011656","article-title":"Concurrent cooperativity and substrate inhibition in the epoxidation of carbamazepine by cytochrome P450 3A4 active site mutants inspired by molecular dynamics simulations","volume":"54","author":"Muller","year":"2015","journal-title":"Biochemistry"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1021\/bi962359z","article-title":"Cooperativity in oxidations catalyzed by cytochrome P450 3A4","volume":"36","author":"Ueng","year":"1997","journal-title":"Biochemistry"},{"key":"ref_39","first-page":"34","article-title":"Aflatoxin B1 oxidation in human CYP1A1 and CYP1A2 cDNA-expressed microsomes","volume":"7","author":"Gallagher","year":"1995","journal-title":"Int. Toxicol. VII Int. Congr. Toxicol."},{"key":"ref_40","first-page":"101","article-title":"Role of human microsomal and human complementary DNA-expressed cytochromes P4501A2 and P4503A4 in the bioactivation of aflatoxin B1","volume":"54","author":"Gallagher","year":"1994","journal-title":"Cancer Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1411","DOI":"10.1093\/carcin\/16.6.1411","article-title":"Metabolism of aflatoxin B1 by rabbit and rat nasal mucosa microsomes and purified cytochrome P450, including isoforms 2A10 and 2A11","volume":"16","author":"Putt","year":"1995","journal-title":"Carcinogenesis"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/S1383-5718(99)00032-7","article-title":"Escherichia coli MTC, a human NADPH P450 reductase competent mutagenicity tester strain for the expression of human cytochrome P450 isoforms 1A1, 1A2, 2A6, 3A4, or 3A5: Catalytic activities and mutagenicity studies","volume":"441","author":"Kranendonk","year":"1999","journal-title":"Mutat. Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1006\/taap.1997.8117","article-title":"Aflatoxin B1 activation in human lung","volume":"144","author":"Kelly","year":"1997","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1093\/annweh\/wxad070","article-title":"Exposure to airborne mycotoxins: The riskiest working environments and tasks","volume":"68","author":"Marcelloni","year":"2024","journal-title":"Ann. Work. Expo. Health"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/0278-6915(84)90050-4","article-title":"Aflatoxin exposures in the industrial setting: An epidemiological study of mortality","volume":"22","author":"Hayes","year":"1984","journal-title":"Food Chem. Toxicol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1021\/mp0600687","article-title":"Gene and protein expression of P-glycoprotein, MRP1, MRP2, and CYP3A4 in the small and large human intestine","volume":"4","author":"Berggren","year":"2007","journal-title":"Mol. Pharm."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1146\/annurev.pharmtox.43.100901.140251","article-title":"Human extrahepatic cytochromes P450: Function in xenobiotic metabolism and tissue-selective chemical toxicity in the respiratory and gastrointestinal tracts","volume":"43","author":"Ding","year":"2003","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1289\/ehp.939999","article-title":"Does aflatoxin exposure in the United Kingdom constitute a cancer risk?","volume":"99","author":"Harrison","year":"1993","journal-title":"Environ. Health Perspect."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1093\/toxsci\/54.1.30","article-title":"Effects of dietary oltipraz and ethoxyquin on aflatoxin B1 biotransformation in non-human primates","volume":"54","author":"Bammler","year":"2000","journal-title":"Toxicol. Sci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1002","DOI":"10.1016\/0006-291X(91)90991-F","article-title":"Isolated hepatocytes are capable of excreting aflatoxin metabolites","volume":"178","author":"Biedrzycka","year":"1991","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2103","DOI":"10.1093\/carcin\/9.11.2103","article-title":"Aflatoxin B1 hydroxylation by the pregnenolone-16 alpha-carbonitrile-inducible form of rat liver microsomal cytochrome P-450","volume":"9","author":"Halvorson","year":"1988","journal-title":"Carcinogenesis"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1021\/tx00028a004","article-title":"Glutathione conjugation of aflatoxin B1 exo- and endo-epoxides by rat and human glutathione S-transferases","volume":"5","author":"Raney","year":"1992","journal-title":"Chem. Res. Toxicol."},{"key":"ref_53","first-page":"2306","article-title":"Oltipraz-mediated changes in aflatoxin B(1) biotransformation in rat liver: Implications for human chemointervention","volume":"56","author":"Buetler","year":"1996","journal-title":"Cancer Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1006\/abbi.1997.9900","article-title":"Mouse cytochrome P450 (Cyp3a11): Predominant expression in liver and capacity to activate aflatoxin B1","volume":"340","author":"Yanagimoto","year":"1997","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1016\/0304-4165(94)90069-8","article-title":"Molecular cloning and functional expression of a mouse cytochrome P-450 (Cyp3a-13): Examination of Cyp3a-13 enzyme to activate aflatoxin B1 (AFB1)","volume":"1201","author":"Yanagimoto","year":"1994","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1002\/mc.2940110204","article-title":"Induction of specific cytochrome P450s involved in aflatoxin B1 metabolism in hepatitis B virus transgenic mice","volume":"11","author":"Kirby","year":"1994","journal-title":"Mol. Carcinog."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/S0300-483X(97)00078-4","article-title":"Effects of co-administration of butylated hydroxytoluene, butylated hydroxyanisole and flavonoids on the activation of mutagens and drug-metabolizing enzymes in mice","volume":"122","author":"Sun","year":"1997","journal-title":"Toxicology"},{"key":"ref_58","first-page":"4752","article-title":"Purified form of cytochrome P-450 from rainbow trout with high activity toward conversion of aflatoxin B1 to aflatoxin B1-2,3-epoxide","volume":"43","author":"Williams","year":"1983","journal-title":"Cancer Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1016\/0304-4165(82)90280-X","article-title":"Purification of cytochromes P-448 from beta-naphthoflavone-treated rainbow trout","volume":"717","author":"Williams","year":"1982","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"3743","DOI":"10.1016\/0006-2952(84)90035-2","article-title":"Benzo[a]pyrene-hydroxylase catalyzed by purified isozymes of cytochrome P-450 from beta-naphthoflavone-fed rainbow trout","volume":"33","author":"Williams","year":"1984","journal-title":"Biochem. Pharmacol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/0141-1136(84)90067-9","article-title":"Cytochrome P-450 isozymes in salmonds determined with antibodies to purifed forms of P-450 from rainbow trout","volume":"14","author":"Williams","year":"1984","journal-title":"Mar. Environ. Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1006\/abbi.1994.1278","article-title":"Cloning and sequencing of the major rainbow trout constitutive cytochrome P450 (CYP2K1): Identification of a new cytochrome P450 gene subfamily and its expression in mature rainbow trout liver and trunk kidney","volume":"312","author":"Buhler","year":"1994","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1016\/0003-9861(84)90414-4","article-title":"Regiospecific hydroxylation of lauric acid at the (omega-1) position by hepatic and kidney microsomal cytochromes P-450 from rainbow trout","volume":"231","author":"Williams","year":"1984","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1279","DOI":"10.1016\/S0090-9556(24)15073-8","article-title":"Heterologous expression of CYP2K1 and identification of the expressed protein (BV-CYP2K1) as lauric acid (omega-1)-hydroxylase and aflatoxin B1 exo-epoxidase","volume":"28","author":"Yang","year":"2000","journal-title":"Drug Metab. Dispos."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1006\/taap.1996.8058","article-title":"In vivo aflatoxin B1 metabolism and hepatic DNA adduction in zebrafish (Danio rerio)","volume":"143","author":"Troxel","year":"1997","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.cbpc.2011.05.013","article-title":"The rainbow trout liver cancer model: Response to environmental chemicals and studies on promotion and chemoprevention","volume":"155","author":"Williams","year":"2012","journal-title":"Comp. Biochem. Physiol. C Toxicol. Pharmacol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/j.cca.2005.02.002","article-title":"CYP2K6 from zebrafish (Danio rerio): Cloning, mapping, developmental\/tissue expression, and aflatoxin B1 activation by baculovirus expressed enzyme","volume":"140","author":"Lee","year":"2005","journal-title":"Comp. Biochem. Physiol. C Toxicol. Pharmacol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/0278-6915(88)90109-3","article-title":"The significance of glutathione conjugation for aflatoxin B1 metabolism in rainbow trout and coho salmon","volume":"26","author":"Valsta","year":"1988","journal-title":"Food Chem. Toxicol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1289\/ehp.8771147","article-title":"Initiation, promotion, and inhibition of carcinogenesis in rainbow trout","volume":"71","author":"Bailey","year":"1987","journal-title":"Environ. Health Perspect."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1919","DOI":"10.1093\/carcin\/9.11.1919","article-title":"Aflatoxin B1 carcinogenesis and its relation to DNA adduct formation and adduct persistence in sensitive and resistant salmonid fish","volume":"9","author":"Bailey","year":"1988","journal-title":"Carcinogenesis"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/0273-2300(89)90014-7","article-title":"Molecular dosimetry of hepatic aflatoxin B1-DNA adducts: Linear correlation with hepatic cancer risk","volume":"10","author":"Bechtel","year":"1989","journal-title":"Regul. Toxicol. Pharmacol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1080\/00071688108447906","article-title":"Susceptibility of various poultry species to dietary aflatoxin","volume":"22","author":"Arafa","year":"1981","journal-title":"Br. Poult. Sci."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1006\/taap.2000.8926","article-title":"Biochemical basis for the extreme sensitivity of turkeys to aflatoxin B(1)","volume":"165","author":"Klein","year":"2000","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.3382\/ps.0741295","article-title":"Effects of feeding fumonisin B1 present in Fusarium moniliforme culture material and aflatoxin singly and in combination to turkey poults","volume":"74","author":"Kubena","year":"1995","journal-title":"Poult. Sci."},{"key":"ref_75","first-page":"55","article-title":"Turkey \u201cX\u201d Disease","volume":"9","author":"Blount","year":"1961","journal-title":"J. Br. Turk. Fed."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"436","DOI":"10.7589\/0090-3558-36.3.436","article-title":"The effect of dietary aflatoxin on wild turkey poults","volume":"36","author":"Quist","year":"2000","journal-title":"J. Wildl. Dis."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1080\/00071660601084390","article-title":"Microsomal and cytosolic biotransformation of aflatoxin B1 in four poultry species","volume":"47","author":"Lozano","year":"2006","journal-title":"Br. Poult. Sci."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/S1532-0456(02)00065-0","article-title":"Biochemical factors underlying the age-related sensitivity of turkeys to aflatoxin B(1)","volume":"132","author":"Klein","year":"2002","journal-title":"Comp. Biochem. Physiol. C Toxicol. Pharmacol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/j.taap.2007.11.017","article-title":"Mechanisms of butylated hydroxytoluene chemoprevention of aflatoxicosis\u2014Inhibition of aflatoxin B1 metabolism","volume":"227","author":"Guarisco","year":"2008","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1021\/tx050233+","article-title":"Molecular cloning and expression of a novel cytochrome p450 from turkey liver with aflatoxin b1 oxidizing activity","volume":"19","author":"Yip","year":"2006","journal-title":"Chem. Res. Toxicol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1159\/000097426","article-title":"Structure and genetic mapping of the Cytochrome P450 gene (CYP1A5) in the turkey (Meleagris gallopavo)","volume":"116","author":"Reed","year":"2007","journal-title":"Cytogenet. Genome Res."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/j.rvsc.2010.04.011","article-title":"Aflatoxin B1 in poultry: Toxicology, metabolism and prevention","volume":"89","author":"Rawal","year":"2010","journal-title":"Res. Vet. Sci."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1322","DOI":"10.1021\/tx1000267","article-title":"Cloning, expression and functional characterization of cytochrome P450 3A37 from turkey liver with high aflatoxin B1 epoxidation activity","volume":"23","author":"Rawal","year":"2010","journal-title":"Chem. Res. Toxicol."},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Dalloul, R.A., Long, J.A., Zimin, A.V., Aslam, L., Beal, K., Blomberg Le, A., Bouffard, P., Burt, D.W., Crasta, O., and Crooijmans, R.P. (2010). Multi-platform next-generation sequencing of the domestic turkey (Meleagris gallopavo): Genome assembly and analysis. PLoS Biol., 8.","DOI":"10.1371\/journal.pbio.1000475"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/j.taap.2011.05.010","article-title":"Metabolism of aflatoxin B1 in turkey liver microsomes: The relative roles of cytochromes P450 1A5 and 3A37","volume":"254","author":"Rawal","year":"2011","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_86","first-page":"259","article-title":"Groundnut toxicity: An examination for toxin in human food products from animals fed toxic groundnut meal","volume":"75","author":"Allcroft","year":"1963","journal-title":"Vet. Rec."},{"key":"ref_87","first-page":"50","article-title":"Toxic Products in Groundnuts. Biological Effects","volume":"2","author":"Allcroft","year":"1963","journal-title":"Chem. Ind."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1038\/202466a0","article-title":"Milk of Mammals Fed an Aflatoxin-Containing Diet","volume":"202","author":"Vles","year":"1964","journal-title":"Nature"},{"key":"ref_89","first-page":"57","article-title":"Cancer risks posed by aflatoxin M1","volume":"16","author":"Hsieh","year":"1985","journal-title":"Princess Takamatsu Symp."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/S0015-6264(67)83060-8","article-title":"Acute toxicity of aflatoxins M1 and M2 in one-day-old ducklings","volume":"5","author":"Purchase","year":"1967","journal-title":"Food Cosmet. Toxicol."},{"key":"ref_91","first-page":"1913","article-title":"Carcinogenicity of dietary aflatoxin M1 in male Fischer rats compared to aflatoxin B1","volume":"47","author":"Cullen","year":"1987","journal-title":"Cancer Res."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1285","DOI":"10.1093\/jnci\/53.5.1285","article-title":"Hepatic carcinogenesis of aflatoxin M1 in rainbow trout (Salmo gairdneri) and its enchancement by cyclopropene fatty acids","volume":"53","author":"Sinnhuber","year":"1974","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1093\/carcin\/9.3.441","article-title":"Comparative metabolism and DNA binding of aflatoxin B1, aflatoxin M1, aflatoxicol and aflatoxicol-M1 in hepatocytes from rainbow trout (Salmo gairdneri)","volume":"9","author":"Loveland","year":"1988","journal-title":"Carcinogenesis"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/S0027-5107(97)00258-3","article-title":"Molecular dosimetry in fish: Quantitative target organ DNA adduction and hepatocarcinogenicity for four aflatoxins by two exposure routes in rainbow trout","volume":"399","author":"Bailey","year":"1998","journal-title":"Mutat. Res."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1006\/taap.1998.8440","article-title":"Metabolism and toxicity of aflatoxins M1 and B1 in human-derived in vitro systems","volume":"151","author":"Neal","year":"1998","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Ali, N., Habib, A., Mahmud, F., Tuba, H.R., and Degen, G.H. (2024). Aflatoxin M(1) Analysis in Urine of Mill Workers in Bangladesh: A Pilot Study. Toxins, 16.","DOI":"10.3390\/toxins16010045"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"3775","DOI":"10.1007\/s00204-020-02857-5","article-title":"Determination of aflatoxin M(1) and deoxynivalenol biomarkers in infants and children urines from Bangladesh","volume":"94","author":"Ali","year":"2020","journal-title":"Arch. Toxicol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"112263","DOI":"10.1016\/j.fct.2021.112263","article-title":"Oncogenic and tumor suppressor pathways in subchronic aflatoxicosis in rats: Association with serum and urinary aflatoxin exposure biomarkers","volume":"153","author":"Apolinario","year":"2021","journal-title":"Food Chem. Toxicol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1080\/19440049.2022.2138559","article-title":"Assessment of aflatoxin M(1) exposure and associated determinants in children from Lahore, Pakistan","volume":"40","author":"Ashraf","year":"2023","journal-title":"Food Addit. Contam. Part A Chem. Anal. Control Expo. Risk Assess."},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Ndaw, S., Remy, A., Jargot, D., Antoine, G., Denis, F., and Robert, A. (2021). Mycotoxins exposure of French grain elevator workers: Biomonitoring and airborne measurements. Toxins, 13.","DOI":"10.3390\/toxins13060382"},{"key":"ref_101","first-page":"3","article-title":"A follow-up study of urinary markers of aflatoxin exposure and liver cancer risk in Shanghai, People\u2019s Republic of China","volume":"3","author":"Qian","year":"1994","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1007\/s12550-019-00355-x","article-title":"Frequency and levels of aflatoxin M(1) in urine of children in Bogota, Colombia","volume":"35","author":"Sanchez","year":"2019","journal-title":"Mycotoxin Res."},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"Sulaiman, S.H., Jamaluddin, R., and Sabran, M.R. (2018). Association between urinary aflatoxin (AFM(1)) and dietary Intake among adults in Hulu Langat district, Selangor, Malaysia. Nutrients, 10.","DOI":"10.3390\/nu10040460"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1093\/carcin\/6.5.675","article-title":"Inhibition of aflatoxin B1-hepatocarcinogenesis in rats by beta-naphthoflavone","volume":"6","author":"Gurtoo","year":"1985","journal-title":"Carcinogenesis"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/0378-4274(91)90195-C","article-title":"Mouse strain differences in glutathione S-transferase activity and aflatoxin B1 biotransformation","volume":"58","author":"Borroz","year":"1991","journal-title":"Toxicol. Lett."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1793","DOI":"10.1093\/carcin\/9.10.1793","article-title":"Comparative effect of dietary butylated hydroxyanisole and beta-naphthoflavone on aflatoxin B1 metabolism, DNA adduct formation, and carcinogenesis in rainbow trout","volume":"9","author":"Goeger","year":"1988","journal-title":"Carcinogenesis"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1016\/0278-6915(83)90140-0","article-title":"Identification and mutagenicity of aflatoxicol-M1 produced by metabolism of aflatoxin B1 and aflatoxicol by liver fractions from rainbow trout (Salmo gairdneri) fed beta-naphthoflavone","volume":"21","author":"Loveland","year":"1983","journal-title":"Food Chem. Toxicol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1080\/0265203031000119025","article-title":"Aflatoxin residues in eggs of laying Japanese quail after long-term administration of rations containing low levels of aflatoxin B1","volume":"20","author":"Oliveira","year":"2003","journal-title":"Food Addit. Contam."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1080\/02652038809373708","article-title":"Long-term administration of low doses of mycotoxins to poultry. 1. Residues of aflatoxin B1 and its metabolites in broilers and laying hens","volume":"5","author":"Micco","year":"1988","journal-title":"Food Addit. Contam."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"3152","DOI":"10.3382\/ps.2014-04240","article-title":"Aflatoxins, hydroxylated metabolites, and aflatoxicol from breast muscle of laying hens","volume":"93","year":"2014","journal-title":"Poult. Sci."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"139","DOI":"10.3109\/00498258709043924","article-title":"Effects of phenobarbital on the biliary excretion of aflatoxin P1-glucuronide and aflatoxin B1-S-glutathione in the rat","volume":"17","author":"Holeski","year":"1987","journal-title":"Xenobiotica"},{"key":"ref_112","first-page":"267","article-title":"Molecular dosimetry in rat urine of aflatoxin-N7-guanine and other aflatoxin metabolites by multiple monoclonal antibody affinity chromatography and immunoaffinity\/high performance liquid chromatography","volume":"52","author":"Groopman","year":"1992","journal-title":"Cancer Res."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1124\/dmd.114.060509","article-title":"Transporter-mediated uptake of UDP-glucuronic acid by human liver microsomes: Assay conditions, kinetics, and inhibition","volume":"43","author":"Rowland","year":"2015","journal-title":"Drug Metab. Dispos."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"27561","DOI":"10.3390\/ijms161126047","article-title":"A Mechanism of O-demethylation of aristolochic acid I by cytochromes P450 and their contributions to this reaction in human and rat livers: Experimental and theoretical approaches","volume":"16","author":"Stiborova","year":"2015","journal-title":"Int. J. Mol. Sci."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1021\/tx00002a004","article-title":"Identification of a novel dihydroxy metabolite of aflatoxin B1 produced in vitro and in vivo in rats and mice","volume":"1","author":"Eaton","year":"1988","journal-title":"Chem. Res. Toxicol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1093\/carcin\/3.11.1261","article-title":"Comparative mutagenicity of aflatoxins using a Salmonella\/trout hepatic enzyme activation system","volume":"3","author":"Coulombe","year":"1982","journal-title":"Carcinogenesis"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"2281","DOI":"10.1073\/pnas.70.8.2281","article-title":"Carcinogens are mutagens: A simple test system combining liver homogenates for activation and bacteria for detection","volume":"70","author":"Ames","year":"1973","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/S0015-6264(75)80006-X","article-title":"Aflaxation B1 hydroxylation by hepatic microsomal preparations from the rhesus monkey","volume":"13","author":"Krieger","year":"1975","journal-title":"Food Cosmet. Toxicol."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1021\/jf60193a048","article-title":"Use of monkey liver microsomes in production of aflatoxin Q1","volume":"22","author":"Hsieh","year":"1974","journal-title":"J. Agric. Food Chem."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1021\/tx00026a009","article-title":"Oxidation of aflatoxins and sterigmatocystin by human liver microsomes: Significance of aflatoxin Q1 as a detoxication product of aflatoxin B1","volume":"5","author":"Raney","year":"1992","journal-title":"Chem. Res. Toxicol."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"8306","DOI":"10.1073\/pnas.87.21.8306","article-title":"Evidence for involvement of multiple forms of cytochrome P-450 in aflatoxin B1 metabolism in human liver","volume":"87","author":"Forrester","year":"1990","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1016\/0041-008X(91)90090-2","article-title":"Bioactivation of aflatoxin B1 by human liver microsomes: Role of cytochrome P450 IIIA enzymes","volume":"108","author":"Ramsdell","year":"1991","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"106996","DOI":"10.1016\/j.envint.2021.106996","article-title":"Mycotoxin exposure biomonitoring in breastfed and non-exclusively breastfed Nigerian children","volume":"158","author":"Ezekiel","year":"2022","journal-title":"Environ. Int."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1002\/ijc.20951","article-title":"Fecal and urinary excretion of aflatoxin B1 metabolites (AFQ1, AFM1 and AFB-N7-guanine) in young Chinese males","volume":"115","author":"Mykkanen","year":"2005","journal-title":"Int. J. Cancer"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"1703","DOI":"10.1124\/dmd.106.009977","article-title":"Characterization of the rhesus monkey CYP3A64 enzyme: Species comparisons of CYP3A substrate specificity and kinetics using baculovirus-expressed recombinant enzymes","volume":"34","author":"Carr","year":"2006","journal-title":"Drug Metab. Dispos."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.taap.2006.12.001","article-title":"Modulation of aflatoxin toxicity and biomarkers by lycopene in F344 rats","volume":"219","author":"Tang","year":"2007","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1093\/toxsci\/kfr240","article-title":"Tissue distribution and gender-divergent expression of 78 cytochrome P450 mRNAs in mice","volume":"124","author":"Renaud","year":"2011","journal-title":"Toxicol. Sci."},{"key":"ref_128","first-page":"133","article-title":"Aflatoxicol as a possible predictor for species sensitivity to aflatoxin B1 (AFB1)","volume":"16","author":"Edwards","year":"1975","journal-title":"Cancer Res."},{"key":"ref_129","first-page":"2058","article-title":"Liver microsomal metabolism of aflatoxin B 1 to a reactive derivative toxic to Salmonella typhimurium TA 1530","volume":"32","author":"Garner","year":"1972","journal-title":"Cancer Res"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"19P","DOI":"10.1042\/bj1250019Pb","article-title":"Hydroxylation and toxicity of aflatoxins","volume":"125","author":"Patterson","year":"1971","journal-title":"Biochem. J."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/S0015-6264(73)80496-1","article-title":"Metabolism as a factor in determining the toxic action of the aflatoxins in different animal species","volume":"11","author":"Patterson","year":"1973","journal-title":"Food Cosmet. Toxicol."},{"key":"ref_132","first-page":"1016","article-title":"Comparative in vitro metabolism of aflatoxicol by liver preparations from animals and humans","volume":"37","author":"Salhab","year":"1977","journal-title":"Cancer Res."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/0041-008X(76)90282-9","article-title":"The role of aflatoxin metabolism in its toxic lesion","volume":"35","author":"Campbell","year":"1976","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1002\/ijc.2910160209","article-title":"The response of Xeroderma pigmentosum cells and controls to the activated mycotoxins, aflatoxins and sterigmatocystin","volume":"16","author":"Stich","year":"1975","journal-title":"Int. J. Cancer"},{"key":"ref_135","doi-asserted-by":"crossref","unstructured":"Murcia, H., and Diaz, G.J. (2020). Dealing with aflatoxin B1 dihydrodiol acute effects: Impact of aflatoxin B1-aldehyde reductase enzyme activity in poultry species tolerant to AFB1 toxic effects. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0235061"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1081\/DMR-100101911","article-title":"Kinetics of hydrolysis and reaction of aflatoxin B1 exo-8,9-epoxide and relevance to toxicity and detoxication","volume":"31","author":"Guengerich","year":"1999","journal-title":"Drug Metab. Rev."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1021\/tx960209j","article-title":"Aflatoxin B1 8,9-epoxide hydrolysis in the presence of rat and human epoxide hydrolase","volume":"10","author":"Johnson","year":"1997","journal-title":"Chem. Res. Toxicol."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1093\/toxsci\/65.1.35","article-title":"Expression of human microsomal epoxide hydrolase in Saccharomyces cerevisiae reveals a functional role in aflatoxin B1 detoxification","volume":"65","author":"Kelly","year":"2002","journal-title":"Toxicol. Sci."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"3309","DOI":"10.1016\/0006-2952(85)90351-X","article-title":"Differential induction of cytochrome P-450-dependent monooxygenase, epoxide hydrolase, glutathione transferase and UDP glucuronosyl transferase activities in the liver of the rainbow trout by beta-naphthoflavone or Clophen A50","volume":"34","author":"Andersson","year":"1985","journal-title":"Biochem. Pharmacol."},{"key":"ref_140","doi-asserted-by":"crossref","unstructured":"Diaz, G.J., and Murcia, H.W. (2019). An unusually high production of hepatic aflatoxin B(1)-dihydrodiol, the possible explanation for the high susceptibility of ducks to aflatoxin B(1). Sci. Rep., 9.","DOI":"10.1038\/s41598-019-44515-6"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1021\/tx010005p","article-title":"Reduction of aflatoxin B1 dialdehyde by rat and human aldo-keto reductases","volume":"14","author":"Guengerich","year":"2001","journal-title":"Chem. Res. Toxicol."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1042\/bj2920013","article-title":"A novel aldehyde reductase with activity towards a metabolite of aflatoxin B1 is expressed in rat liver during carcinogenesis and following the administration of an anti-oxidant","volume":"292","author":"Judah","year":"1993","journal-title":"Biochem. J."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1093\/carcin\/bgg016","article-title":"Characterization of the rat aflatoxin B1 aldehyde reductase gene, AKR7A1. Structure and chromosomal localization of AKR7A1 as well as identification of antioxidant response elements in the gene promoter","volume":"24","author":"Ellis","year":"2003","journal-title":"Carcinogenesis"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1093\/carcin\/20.7.1215","article-title":"cDNA cloning, expression and activity of a second human aflatoxin B1-metabolizing member of the aldo-keto reductase superfamily, AKR7A3","volume":"20","author":"Knight","year":"1999","journal-title":"Carcinogenesis"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1042\/bj3120535","article-title":"Substrate specificity of an aflatoxin-metabolizing aldehyde reductase","volume":"312","author":"Ellis","year":"1995","journal-title":"Biochem. J."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1006\/taap.1994.1045","article-title":"The primary and secondary metabolism of aflatoxin B1 by rat hepatocytes cultured on matrigel","volume":"125","author":"Judah","year":"1994","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1021\/tx700397n","article-title":"Quantification of urinary aflatoxin B1 dialdehyde metabolites formed by aflatoxin aldehyde reductase using isotope dilution tandem mass spectrometry","volume":"21","author":"Johnson","year":"2008","journal-title":"Chem. Res. Toxicol."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1093\/toxsci\/kfp003","article-title":"Transgenic expression of aflatoxin aldehyde reductase (AKR7A1) modulates aflatoxin B1 metabolism but not hepatic carcinogenesis in the rat","volume":"109","author":"Roebuck","year":"2009","journal-title":"Toxicol. Sci."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/j.toxicon.2005.03.023","article-title":"Comparative activities of glutathione-S-transferase and dialdehyde reductase toward aflatoxin B1 in livers of experimental and farm animals","volume":"46","author":"Tulayakul","year":"2005","journal-title":"Toxicon"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1016\/0041-008X(87)90132-3","article-title":"Comparative effects of butylated hydroxyanisole on hepatic in vivo DNA binding and in vitro biotransformation of aflatoxin B1 in the rat and mouse","volume":"90","author":"Monroe","year":"1987","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/0041-008X(88)90342-0","article-title":"Effects of modulation of hepatic glutathione on biotransformation and covalent binding of aflatoxin B1 to DNA in the mouse","volume":"94","author":"Monroe","year":"1988","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1097\/00008571-199508000-00006","article-title":"Human variability in hepatic glutathione S-transferase-mediated conjugation of aflatoxin B1-epoxide and other substrates","volume":"5","author":"Slone","year":"1995","journal-title":"Pharmacogenetics"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"2613","DOI":"10.1093\/carcin\/14.12.2613","article-title":"In vitro metabolism of aflatoxin B1 by normal and tumorous liver tissue from Thailand","volume":"14","author":"Kirby","year":"1993","journal-title":"Carcinogenesis"},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1093\/toxsci\/49.2.156","article-title":"Concise review of the glutathione S-transferases and their significance to toxicology","volume":"49","author":"Eaton","year":"1999","journal-title":"Toxicol. Sci."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"445","DOI":"10.3109\/10409239509083491","article-title":"The glutathione S-transferase supergene family: Regulation of GST and the contribution of the isoenzymes to cancer chemoprotection and drug resistance","volume":"30","author":"Hayes","year":"1995","journal-title":"Crit. Rev. Biochem. Mol. Biol."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"3056","DOI":"10.1021\/bi962537o","article-title":"Conjugation of highly reactive aflatoxin B1 exo-8,9-epoxide catalyzed by rat and human glutathione transferases: Estimation of kinetic parameters","volume":"36","author":"Johnson","year":"1997","journal-title":"Biochemistry"},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1093\/toxsci\/kfq135","article-title":"Sulforaphane- and phenethyl isothiocyanate-induced inhibition of aflatoxin B1-mediated genotoxicity in human hepatocytes: Role of GSTM1 genotype and CYP3A4 gene expression","volume":"116","author":"Stapleton","year":"2010","journal-title":"Toxicol. Sci."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"2384","DOI":"10.1073\/pnas.92.6.2384","article-title":"Susceptibility to hepatocellular carcinoma is associated with genetic variation in the enzymatic detoxification of aflatoxin B1","volume":"92","author":"McGlynn","year":"1995","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"1971","DOI":"10.1093\/carcin\/20.10.1971","article-title":"Glutathione S-transferase-catalyzed conjugation of bioactivated aflatoxin B(1) in human lung: Differential cellular distribution and lack of significance of the GSTM1 genetic polymorphism","volume":"20","author":"Stewart","year":"1999","journal-title":"Carcinogenesis"},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1093\/toxsci\/56.1.26","article-title":"Mu-class GSTs are responsible for aflatoxin B(1)-8, 9-epoxide-conjugating activity in the nonhuman primate macaca fascicularis liver","volume":"56","author":"Wang","year":"2000","journal-title":"Toxicol. Sci."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1093\/toxsci\/70.1.20","article-title":"Complementary DNA cloning, protein expression, and characterization of alpha-class GSTs from Macaca fascicularis liver","volume":"70","author":"Wang","year":"2002","journal-title":"Toxicol. Sci."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/0009-2797(78)90129-1","article-title":"The major metabolite of aflatoxin B1 in the rat is a glutathione conjugate","volume":"22","author":"Degen","year":"1978","journal-title":"Chem. Biol. Interact."},{"key":"ref_163","unstructured":"Eaton, D.L., and Groopman, J.D. (1995). Biotransformation of Aflatoxins. The Toxicology of Aflatoxins: Human Health, Veterinary and Agricultural Significance, Academic Press."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1042\/bj3180075","article-title":"Characterization of the rat glutathione S-transferase Yc2 subunit gene, GSTA5: Identification of a putative antioxidant-responsive element in the 5\u2032-flanking region of rat GSTA5 that may mediate chemoprotection against aflatoxin B1","volume":"318","author":"Pulford","year":"1996","journal-title":"Biochem. J."},{"key":"ref_165","first-page":"4573","article-title":"Enzymatic characteristics of chimeric mYc\/rYc1 glutathione S-transferases","volume":"54","author":"Buetler","year":"1994","journal-title":"Cancer Res."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1006\/taap.1998.8493","article-title":"Identification of amino acid residues essential for high aflatoxin B1-8,9-epoxide conjugation activity in alpha class glutathione S-transferases through site-directed mutagenesis","volume":"152","author":"McHugh","year":"1998","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"20707","DOI":"10.1016\/S0021-9258(17)32050-1","article-title":"Cloning of cDNAs from fetal rat liver encoding glutathione S-transferase Yc polypeptides. The Yc2 subunit is expressed in adult rat liver resistant to the hepatocarcinogen aflatoxin B1","volume":"269","author":"Hayes","year":"1994","journal-title":"J. Biol. Chem."},{"key":"ref_168","first-page":"3887","article-title":"Resistance to aflatoxin B1 is associated with the expression of a novel aldo-keto reductase which has catalytic activity towards a cytotoxic aldehyde-containing metabolite of the toxin","volume":"53","author":"Hayes","year":"1993","journal-title":"Cancer Res."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1016\/0163-7258(91)90053-O","article-title":"Contribution of the glutathione S-transferases to the mechanisms of resistance to aflatoxin B1","volume":"50","author":"Hayes","year":"1991","journal-title":"Pharmacol. Ther."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1093\/carcin\/13.1.95","article-title":"Potent inhibition of aflatoxin-induced hepatic tumorigenesis by the monofunctional enzyme inducer 1,2-dithiole-3-thione","volume":"13","author":"Kensler","year":"1992","journal-title":"Carcinogenesis"},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"2488","DOI":"10.1158\/0008-5472.CAN-05-3823","article-title":"Potent protection against aflatoxin-induced tumorigenesis through induction of Nrf2-regulated pathways by the triterpenoid 1-[2-cyano-3-,12-dioxooleana-1,9(11)-dien-28-oyl]imidazole","volume":"66","author":"Yates","year":"2006","journal-title":"Cancer Res."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1093\/carcin\/bgx048","article-title":"Characterization of liver injury, oval cell proliferation and cholangiocarcinogenesis in glutathione S-transferase A3 knockout mice","volume":"38","author":"Crawford","year":"2017","journal-title":"Carcinogenesis"},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/j.taap.2009.10.008","article-title":"Glutathione-S-transferase A3 knockout mice are sensitive to acute cytotoxic and genotoxic effects of aflatoxin B1","volume":"242","author":"Ilic","year":"2010","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_174","first-page":"314","article-title":"Complementary DNA cloning, messenger RNA expression, and induction of alpha-class glutathione S-transferases in mouse tissues","volume":"52","author":"Buetler","year":"1992","journal-title":"Cancer Res."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.1124\/mol.64.5.1018","article-title":"Expression of the aflatoxin B1-8,9-epoxide-metabolizing murine glutathione S-transferase A3 subunit is regulated by the Nrf2 transcription factor through an antioxidant response element","volume":"64","author":"Jowsey","year":"2003","journal-title":"Mol. Pharmacol."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.gene.2009.11.001","article-title":"Comparative genomics identifies new alpha class genes within the avian glutathione S-transferase gene cluster","volume":"452","author":"Kim","year":"2010","journal-title":"Gene"},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1093\/toxsci\/kfr212","article-title":"Functional characterization of alpha-class glutathione s-transferases from the Turkey (Meleagris gallopavo)","volume":"124","author":"Kim","year":"2011","journal-title":"Toxicol. Sci."},{"key":"ref_178","doi-asserted-by":"crossref","unstructured":"Kim, J.E., Bunderson, B.R., Croasdell, A., Reed, K.M., and Coulombe, R.A. (2013). Alpha-class glutathione S-transferases in wild turkeys (Meleagris gallopavo): Characterization and role in resistance to the carcinogenic mycotoxin aflatoxin B1. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0060662"},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.cbpc.2013.05.007","article-title":"Heterologous expression and functional characterization of avian mu-class glutathione S-transferases","volume":"158","author":"Bunderson","year":"2013","journal-title":"Comp. Biochem. Physiol. C Toxicol. Pharmacol."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/S0009-2797(85)80124-1","article-title":"The mercapturic acid pathway metabolites of a glutathione conjugate of aflatoxin B1","volume":"55","author":"Moss","year":"1985","journal-title":"Chem. Biol. Interact."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1124\/pr.109.002014","article-title":"Xenobiotic, bile acid, and cholesterol transporters: Function and regulation","volume":"62","author":"Klaassen","year":"2010","journal-title":"Pharmacol. Rev."},{"key":"ref_182","first-page":"287","article-title":"Hepatic glutathione and glutathione S-conjugate transport mechanisms","volume":"70","author":"Lee","year":"1997","journal-title":"Yale J. Biol. Med."},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1093\/carcin\/5.7.869","article-title":"Effect of manipulation of gamma-glutamyl transpeptidase levels on biliary excretion of aflatoxin B1 conjugates","volume":"5","author":"Moss","year":"1984","journal-title":"Carcinogenesis"},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"1144","DOI":"10.1021\/tx960161+","article-title":"Synthesis and characterization of aflatoxin B1 mercapturic acids and their identification in rat urine","volume":"10","author":"Scholl","year":"1997","journal-title":"Chem. Res. Toxicol."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1093\/toxsci\/kfu056","article-title":"Genetic or pharmacologic activation of Nrf2 signaling fails to protect against aflatoxin genotoxicity in hypersensitive GSTA3 knockout mice","volume":"139","author":"Kensler","year":"2014","journal-title":"Toxicol. Sci."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1093\/jaoac\/92.2.487","article-title":"Synthesis and characterization of mercapturic acid (N-acetyl-L-cysteine)-aflatoxin B1 adduct and its quantitation in rat urine by an enzyme immunoassay","volume":"92","author":"Nayak","year":"2009","journal-title":"J. AOAC Int."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1093\/jnci\/91.4.347","article-title":"Protective alterations in phase 1 and 2 metabolism of aflatoxin B1 by oltipraz in residents of Qidong, People\u2019s Republic of China","volume":"91","author":"Wang","year":"1999","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_188","first-page":"5501","article-title":"Protection against aflatoxin B1-induced hepatocarcinogenesis in F344 rats by 5-(2-pyrazinyl)-4-methyl-1,2-dithiole-3-thione (oltipraz): Predictive role for short-term molecular dosimetry","volume":"51","author":"Roebuck","year":"1991","journal-title":"Cancer Res."},{"key":"ref_189","doi-asserted-by":"crossref","unstructured":"Kensler, T.W., and Eaton, D.L. (2024). 65 Years on-Aflatoxin Biomarkers Blossoming: Whither Next?. Toxins, 16.","DOI":"10.3390\/toxins16110496"},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/0300-483X(84)90133-1","article-title":"Increase in glucuronide conjugation of aflatoxin P1 after pretreatment with microsomal enzyme inducers","volume":"32","author":"Ehrich","year":"1984","journal-title":"Toxicology"},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1016\/0278-6915(85)90282-0","article-title":"Characterization of water-soluble glucuronide and sulphate conjugates of aflatoxin B1. 2. Studies in primary cultures of rat hepatocytes","volume":"23","author":"Wei","year":"1985","journal-title":"Food Chem. Toxicol."},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1016\/0278-6915(85)90281-9","article-title":"Characterization of water-soluble glucuronide and sulphate conjugates of aflatoxin B1. 1. Urinary excretion in monkey, rat and mouse","volume":"23","author":"Wei","year":"1985","journal-title":"Food Chem. Toxicol."},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1128\/am.28.6.1027-1029.1974","article-title":"Further characterization of tissue distribution and metabolism of (14C)aflatoxin B1 in chickens","volume":"28","author":"Chipley","year":"1974","journal-title":"Appl. Microbiol."},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1126\/science.171.3971.584","article-title":"Aflatoxin P-1: A new aflatoxin metabolite in monkeys","volume":"171","author":"Dalezios","year":"1971","journal-title":"Science"},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1016\/S0015-6264(73)80331-1","article-title":"Excretion and metabolism of orally administered aflatoxin B1 by rhesus monkeys","volume":"11","author":"Dalezios","year":"1973","journal-title":"Food Cosmet. Toxicol."},{"key":"ref_196","first-page":"2297","article-title":"Metabolism of aflatoxin B 1 in rhesus monkeys","volume":"32","author":"Dalezios","year":"1972","journal-title":"Cancer Res."},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1016\/0278-6915(83)90103-5","article-title":"Metabolite distribution and rate of residue clearance in turkeys fed a diet containing aflatoxin B1","volume":"21","author":"Gregory","year":"1983","journal-title":"Food Chem. Toxicol."},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1016\/0278-6915(84)90272-2","article-title":"Effect of dietary selenium on the metabolism of aflatoxin B1 in turkeys","volume":"22","author":"Gregory","year":"1984","journal-title":"Food Chem. Toxicol."},{"key":"ref_199","first-page":"45","article-title":"Characterization and mutagenciity of water-soluble conjugates of aflatoxin B1","volume":"45","author":"Wei","year":"1978","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_200","doi-asserted-by":"crossref","unstructured":"EFSA Panel on Contaminants in the Food Chain (CONTAM), Schrenk, D., Bignami, M., Bodin, L., Chipman, J.K., Del Mazo, J., Grasl-Kraupp, B., Hogstrand, C., Hoogenboom, L.R., and Leblanc, J.C. (2020). Risk assessment of aflatoxins in food. 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