Aflatoxin B1 DNA-Adducts in Hepatocellular Carcinoma from a Low Exposure Area

Nutrients. 2022 Apr 15;14(8):1652. doi: 10.3390/nu14081652.

Abstract

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.

Keywords: AFB1; CD68; HCC; cholangiocarcinoma; food control.

MeSH terms

  • Aflatoxin B1 / toxicity
  • Animals
  • Carcinoma, Hepatocellular* / etiology
  • Cholangiocarcinoma* / complications
  • DNA Adducts / adverse effects
  • Liver Cirrhosis / complications
  • Liver Neoplasms* / etiology
  • Rats

Substances

  • DNA Adducts
  • Aflatoxin B1