Does anatoxin B-1 play a role in the etiology of hepatocellular carcinoma in the United States?

Previous research showed that risk factors associated with hepatocellular c arcinoma (HCC) include infection with hepatitis B (HBV) and hepatitis C (HC V) viruses, exposure to aflatoxin B-1 (AFB(1)), and liver cirrhosis, due pr imarily to alcohol consumption. To determine whether AFB(1) may play a role in HCC in the United States, a search for AFB(1) adducts and p53 alteratio ns, potentially induced by AFB(1), was conducted in the United States in 23 HCC patients with available tissue samples. The presence of AFB(1), tumor- DNA and -serum lysine adducts and mutant p53 product was determined by immu noassays and codon 249 p53 mutation by restriction enzyme analysis. HBV and HCV serology and serum HBV-DNA were also determined. Thirteen patients wer e positive for HBV by HBs antigen or anti-HBc antigen or by polymerase chai n reaction for HBV-DNA sequences. Nine patients were free of HBV and HCV ma rkers; 5 of 22 sera tested were anti-HCV positive, p53 Protein expression, determined by immunohistochemical staining, was present in 5 of the 23 tumo r tissues, whereas p53 codon 249 mutations were not observed in the 5 cases in which tissue was available for study. AFB(1) tumor-DNA adducts were pre sent in 3 of 19 tumor tissues, and in 1 of these 3 samples p53 protein was also detected. Sera from only 5 of the patients were tested for AFB(1)-lysi ne adducts, and all were positive. Irt these five patients, neither p53 pro tein nor a mutation on. codon 249 was detected. The demonstration that AFB( 1)-DNA and -lysine adducts are present in HCC patients in the United States is intriguing but requires further substantiation because of the small num ber of subjects in this pilot study. To elucidate the pathogenetic signific ance of these findings, further investigation, including studies in larger patient cohorts and properly selected controls, is warranted.