Rat hepatoma cells show extreme sensitivity to aflatoxin B1

Aflatoxin B₁ (Afl B₁) is a potent hepatotoxin and hepatocarcinogen that requires metabolic activation to exert its cytotoxic and genotoxic effects. FU-5 cells are a rat hepatoma cell line originally derived from Reuber hepatoma cells. We found that the FU-5 cell line and an FAO-1 subclone showed extreme sensitivity to Afl B₁. However, the FAO-1 line was about 50 times more sensitive to Afl B₁ cytotoxicity compared with the parental FU-5 line. Upon exposure to Afl B₁, the FAO-1 line produced one major metabolite, which we identified as Aflatoxicol (AFl R₀). In constrast, the FU-5 line produced Afl R₀ and many polar metabolites that may be detoxification products. The FAO-1 cell bound slightly more Afl B₁ to its DNA than did the FU-5 line. The differences in metabolism of Afl B₁ may account for the differential cytotoxicity that this mycotoxin exerted on FAO-1 and FU-5 cells. Although both hepatoma cell lines were efficient at converting Afl B₁ into cytotoxic metabolites, they bound small amounts of Afl B₁ to their DNA and were inefficient in converting Afl B₁ into mutagenic metabolites. In addition, both lines were incapable of converting 2-acetylaminofluorene, benzo(a)pyrene, and dimethylnitrosamine into cytotoxic metabolites.