{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T01:57:42Z","timestamp":1792547862480,"version":"4.5.0"},"reference-count":21,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2022,4,15]],"date-time":"2022-04-15T00:00:00Z","timestamp":1649980800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Aflatoxin B1 (AFB1) is a class 1 carcinogen with an ascertained role in the development of hepatocellular carcinoma (HCC) in high exposure areas. Instead, this study aimed to assay whether chronic\/intermittent, low-dose AFB1 consumption might occur in low-exposure geographical areas, ultimately accumulating in the liver and possibly contributing to liver cancer. AFB1-DNA adducts were assayed by immunostaining in liver tissues from three Italian series of twenty cirrhosis without HCC, 131 HCC, and 45 cholangiocarcinoma, and in an AFB1-induced HCC rat model. CD68, TP53 immunostaining, and TP53 RFLP analysis of R249S transversion were used to characterize cell populations displaying AFB1-DNA adducts. Twenty-five HCCs displayed AFB1-adducts both in neoplastic hepatocytes and in cells infiltrating the tumor and non-tumor tissues. Nuclear immunostaining was observed in a few cases, while most cases showed cytoplasmic immunostaining, especially in CD68-positive tumor-infiltrating cells, suggestive for phagocytosis of dead hepatocytes. Similar patterns were observed in AFB1-induced rat HCC, though with higher intensity. Cholangiocarcinoma and cirrhosis without HCC did not displayAFB1-adducts, except for one case. Despite not providing a causal relationship with HCC, these findings still suggest paying attention to detection and control measures for aflatoxins to ensure food safety in low exposure areas.<\/jats:p>","DOI":"10.3390\/nu14081652","type":"journal-article","created":{"date-parts":[[2022,4,19]],"date-time":"2022-04-19T01:03:01Z","timestamp":1650330181000},"page":"1652","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Aflatoxin B1 DNA-Adducts in Hepatocellular Carcinoma from a Low Exposure Area"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5187-9559","authenticated-orcid":false,"given":"Laura","family":"Gramantieri","sequence":"first","affiliation":[{"name":"Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4591-5699","authenticated-orcid":false,"given":"Federica","family":"Gnudi","sequence":"additional","affiliation":[{"name":"Cesare Maltoni Cancer Research Center, Ramazzini Institute, Via Saliceto 3, 40010 Bentivoglio, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Vasuri","sequence":"additional","affiliation":[{"name":"Pathology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniele","family":"Mandrioli","sequence":"additional","affiliation":[{"name":"Cesare Maltoni Cancer Research Center, Ramazzini Institute, Via Saliceto 3, 40010 Bentivoglio, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4302-4411","authenticated-orcid":false,"given":"Francesca","family":"Fornari","sequence":"additional","affiliation":[{"name":"Department for Life Quality Studies, University of Bologna, 40126 Rimini, Italy"},{"name":"Center for Applied Biomedical Research (CRBA), University of Bologna, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8350-1155","authenticated-orcid":false,"given":"Francesco","family":"Tovoli","sequence":"additional","affiliation":[{"name":"Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy"},{"name":"Cesare Maltoni Cancer Research Center, Ramazzini Institute, Via Saliceto 3, 40010 Bentivoglio, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabrizia","family":"Suzzi","sequence":"additional","affiliation":[{"name":"Center for Applied Biomedical Research (CRBA), University of Bologna, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1823-2865","authenticated-orcid":false,"given":"Andrea","family":"Vornoli","sequence":"additional","affiliation":[{"name":"Cesare Maltoni Cancer Research Center, Ramazzini Institute, Via Saliceto 3, 40010 Bentivoglio, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonia","family":"D\u2019Errico","sequence":"additional","affiliation":[{"name":"Pathology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy"},{"name":"Department of Experimental, Diagnostic and Specialty Medicine, University di Bologna, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8264-1845","authenticated-orcid":false,"given":"Fabio","family":"Piscaglia","sequence":"additional","affiliation":[{"name":"Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy"},{"name":"Department of Medical and Surgical Science, University of Bologna, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1904-1577","authenticated-orcid":false,"given":"Catia","family":"Giovannini","sequence":"additional","affiliation":[{"name":"Center for Applied Biomedical Research (CRBA), University of Bologna, 40138 Bologna, Italy"},{"name":"Department of Experimental, Diagnostic and Specialty Medicine, University di Bologna, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"818","DOI":"10.1289\/ehp.0901388","article-title":"Global burden of aflatoxin-induced hepatocellular carcinoma: A risk assessment","volume":"118","author":"Liu","year":"2010","journal-title":"Environ. 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