{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,2]],"date-time":"2026-01-02T17:22:29Z","timestamp":1767374549602,"version":"build-2065373602"},"reference-count":30,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2010,3,31]],"date-time":"2010-03-31T00:00:00Z","timestamp":1269993600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>The potent experimental renal carcinogenesis of ochratoxin A (OTA) in male rats makes the dietary contaminant a potential factor in human oncology. We explored whether the tumour promoter sodium barbitate could shorten the otherwise long latency between exposure to toxin and tumourigenesis. Young rats, of a hybrid in which mononuclear leukaemia was rare, were given feed contaminated (5 ppm) with OTA for 36 weeks to initiate renal tumourigenesis. Some individuals were thereafter given sodium barbitate (500 ppm in drinking water) for life. Pathological outcomes were studied at or near the end of natural life. Renal tumours in males given barbitate became evident after latency of one year, but only slightly before those without barbitate. In contrast, female mammary tumourigenesis was advanced by at least 6 months synchronously in all rats given the OTA-barbitate regimen compared to tumourigenesis in controls. Diagnosis of malignant mammary angiosarcoma in a female given the OTA-barbitate regimen is a new finding in the rat. The long latency of OTA-induced renal tumourigenesis was not notably susceptible to accelerated promotion by barbitate, contrasting with an apparently marked effect of barbitate on development of mammary tumours.<\/jats:p>","DOI":"10.3390\/toxins2040552","type":"journal-article","created":{"date-parts":[[2010,3,31]],"date-time":"2010-03-31T11:10:34Z","timestamp":1270033834000},"page":"552-571","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Oncological Outcomes in Rats Given Nephrocarcinogenic Exposure to Dietary Ochratoxin A, Followed by the Tumour Promoter Sodium Barbital for Life: A Pilot Study"],"prefix":"10.3390","volume":"2","author":[{"given":"Peter G.","family":"Mantle","sequence":"first","affiliation":[{"name":"Centre for Environmental Policy, Imperial College London, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miloslav","family":"Dobrota","sequence":"additional","affiliation":[{"name":"Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cheryl E.","family":"Gillett","sequence":"additional","affiliation":[{"name":"Hedley Atkins Breast Pathology Laboratory, Guy\u2019s Hospital, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edward W.","family":"Odell","sequence":"additional","affiliation":[{"name":"Department of Oral Pathology, King\u2019s College London, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah E.","family":"Pinder","sequence":"additional","affiliation":[{"name":"Department of Academic Oncology, Guy\u2019s Hospital, London. UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2010,3,31]]},"reference":[{"key":"ref_1","unstructured":"Boorman, G.A. (1989). Toxicology and Carcinogenesis Studies of Ochratoxin A (CAS No. 303-47-9) in F344\/N Rats (Gavage Studies), Technical Report 358, Research Triangle Park."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1002\/(SICI)1097-0215(19980703)77:1<70::AID-IJC12>3.0.CO;2-D","article-title":"Strain- and sex-specific induction of renal tumours by ochratoxin A in rats correlates with DNA adduction","volume":"77","author":"Castegnaro","year":"1998","journal-title":"Int. J. Cancer"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1080\/02652030500358431","article-title":"Renal tumourigenesis in male rats in response to chronic dietary ochratoxin A","volume":"22 (Suppl. 1)","author":"Mantle","year":"2005","journal-title":"Food Addit. Contam."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1808","DOI":"10.1016\/j.fct.2008.01.020","article-title":"Interpretation of pharmacodynamics of ochratoxin A in blood plasma of rats, during and after acute or chronic ingestion","volume":"46","author":"Mantle","year":"2008","journal-title":"Food Chem. Toxicol."},{"key":"ref_5","first-page":"679","article-title":"Enhancing effect of phenobarbital on the development of enzyme-altered islands and hepatocellular carcinomas initiated by 3-methyl-4-(dimethylamino)azobenzene or diethyl-nitrosamine","volume":"69","author":"Kitagawa","year":"1978","journal-title":"Gann"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1311","DOI":"10.1093\/jnci\/61.5.1311","article-title":"Enhancement of rat hepatocellular-altered foci by the liver promoter phenobarbital: Evidence that foci are precursors of neoplasms and that the promoter acts as carcinogen-induced lesions","volume":"61","author":"Watanabe","year":"1978","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1093\/carcin\/4.2.141","article-title":"Phenobarbital as a promoter in the initiation\/selection process of experimental rat hepatocarcinogenesis","volume":"4","author":"Lans","year":"1983","journal-title":"Carcinogenesis"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1093\/carcin\/11.4.647","article-title":"Initiation by nickel(ll) acetate and promotion by sodium barbital of renal cortical epithelial tumours in male F344 rats","volume":"11","author":"Kasprzak","year":"1990","journal-title":"Carcinogenesis"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1553","DOI":"10.1093\/carcin\/21.8.1553","article-title":"Promotion by sodium barbital induces early development but does not increase the multiplicity of hereditary renal tumours in Eker rats","volume":"21","author":"Wolf","year":"1990","journal-title":"Carcinogenesis"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"4052","DOI":"10.1158\/0008-5472.CAN-06-3587","article-title":"Carcinogen-specific gene expression profiles in short-term treated Eker and wild-type rats indicative of pathways involved in renal tumorigenesis","volume":"67","author":"Stemmer","year":"2007","journal-title":"Cancer Res."},{"key":"ref_11","unstructured":"Burtis, C.A., Ashwood, E.R., and Bruns, D.E. (2005). Tietz fundamentals of clinical chemistry, WB Saunders Company."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1016\/j.oraloncology.2004.10.009","article-title":"Heterogeneity, histological features and DNA ploidy in oral carcinoma by image-based analysis","volume":"41","author":"Diwakar","year":"2005","journal-title":"Oral Oncol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/S0091-679X(08)61721-5","article-title":"DNA analysis from paraffin-embedded blocks","volume":"41","author":"Hedley","year":"1994","journal-title":"Method Cell Biol."},{"key":"ref_14","unstructured":"Howard, P.C. (2001). Technical report on the toxicology and carcinogenesis studies of Fumonisin B1 (CAS No. 116355-83-0) in F344\/N rats and B6C3F-1 mice (feed studies), Report number 496, Research Triangle Park."},{"key":"ref_15","first-page":"41","article-title":"Spontaneous leukaemia in Fischer rats","volume":"30","author":"Moloney","year":"1970","journal-title":"Cancer Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"719","DOI":"10.3390\/ijms9050719","article-title":"Binding of ochratoxin A to a urinary globulin; a new concept to account for gender difference in rat nephrocarcinogenic responses","volume":"9","author":"Mantle","year":"2008","journal-title":"Int. J. Mol. Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.etp.2007.05.001","article-title":"DNA ploidy distribution in renal tumours induced in male rats by dietary ochratoxin A","volume":"59","author":"Brown","year":"2007","journal-title":"Exp. Toxicol. Pathol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1921","DOI":"10.1016\/j.fct.2009.05.003","article-title":"A different kinetic profile of ochratoxin A in mature male rats","volume":"47","author":"Vettorazzi","year":"2009","journal-title":"Food Chem. Toxicol."},{"key":"ref_19","first-page":"72","article-title":"Blood volume in the rat","volume":"25","author":"Lee","year":"1985","journal-title":"J. Nuclear Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.taap.2008.02.018","article-title":"Gene expression changes induced by ochratoxin A in renal and hepatic tissues of male F344 rat after oral repeated administration","volume":"230","author":"Arbillaga","year":"2008","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1002\/ijc.11069","article-title":"Strain-specific mammary proliferation lesion development following lifetime oral administration of ochratoxin A in DA and Lewis rats","volume":"105","author":"Son","year":"2003","journal-title":"Int. J. Cancer"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1002\/ijc.20508","article-title":"Ochratoxin study","volume":"112","author":"Castegnaro","year":"2004","journal-title":"Int. J. Cancer"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1002\/(SICI)1098-2744(199810)23:2<76::AID-MC4>3.0.CO;2-B","article-title":"Sex- and strain-specific expression of cytochrome P450s in ochratoxin A-induced genotoxicity and carcinogenicity in rats","volume":"23","author":"Pinelli","year":"1998","journal-title":"Molec. Carcinog."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.1093\/jnci\/50.5.1243","article-title":"Comparison of neoplasms from six sources of rats","volume":"50","author":"Mackenzie","year":"1973","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_25","first-page":"449","article-title":"Spontaneous mammary tumours in ageing Noble rats","volume":"22","author":"Cheung","year":"2003","journal-title":"Int. J. Oncol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1016\/j.cvex.2004.04.009","article-title":"Spontaneous tumours of small mammals","volume":"7","author":"Greenacre","year":"2004","journal-title":"Vet. Clin. N. Amer. Exot. Anim. Pract."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1080\/01926230701748156","article-title":"Histopathology of hemangiosarcomas in mice and hamsters and liposarcomas\/fibrosarcomas in rats associated with PPAR agonists","volume":"35","author":"Hardisty","year":"2007","journal-title":"Toxicol. Pathol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1080\/15287390500195570","article-title":"Ochratoxin A: Its cancer risk and potential for exposure","volume":"9","author":"Clark","year":"2006","journal-title":"J. Toxicol. Environ. Health Part B"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1021\/tx900295a","article-title":"Structures of covalent adducts between DNA and ochratoxin A: A new factor in debate about genotoxicity and human risk assessment","volume":"23","author":"Mantle","year":"2010","journal-title":"Chem. Res. Toxicol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2419","DOI":"10.1016\/j.fct.2009.05.043","article-title":"Minimum tolerable exposure period and maximum threshold dietary intake for causing renal cancer in Dark Agouti rats","volume":"47","author":"Mantle","year":"2009","journal-title":"Food Chem.Toxicol."}],"container-title":["Toxins"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6651\/2\/4\/552\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T22:02:00Z","timestamp":1760220120000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6651\/2\/4\/552"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,3,31]]},"references-count":30,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2010,4]]}},"alternative-id":["toxins2040552"],"URL":"https:\/\/doi.org\/10.3390\/toxins2040552","relation":{},"ISSN":["2072-6651"],"issn-type":[{"type":"electronic","value":"2072-6651"}],"subject":[],"published":{"date-parts":[[2010,3,31]]}}}