The activation of aflatoxin B1 in liver slices and in bacterial mutagenicity assays using livers from different species including man

The activation of aflatoxin B 1 (AFB 1 ) has been compared in two in vitro systems: (1) binding to DNA in liver slices incubated with [ 14 C] or [ 3 H]AFB 1 ; (2) standard bacterial mutation systems using 9000 x g supernatant (S-9) fractions from uninduced livers for activation. Several factors which modify aflatoxin carcinogenesis were investigated, namely species, sex, phenobarbitone pretreatment and aflatoxin G 1 (AFG 1 ) compared with AFB 1 . The results from DNA binding in liver slices showed the following trends: rat > hamster > mouse, control > phenobarbitone-pretreated rat and AFB 1 > AFG 1 which correlated directly with trends in carcinoenicity. An exception to this trend was the similar level of binding found in male and female rat livers, the latter being less susceptible to AFB 1 carcinogenesis. This result suggests that sex differences in AFB 1 carcinogenicity may be due to differences in repair of lesions or during the promotion phase of carcinogenesis. The levels of binding of [ 3 H]AFB 1 to DNA slices from fresh human liver biopsies showed considerable variation between the six samples. Values ranged from 0.7–8.5 ng AFB 1 /mg DNA, which are in between values observed in the hamster and mouse. Mutagenicity data did not correlate with carcinogenicity in relation to species differences (hamster > rat > mouse) nor phenobarbitone pretreatment. Supplementation of the top agar mixture with glutathione and/or pre-incubation of S-9, AFB 1 and cofactors did not improve this correlation. Nevertheless, it is expected that differences between these two systems are due to limitations of the metabolizing system in mutagenicity tests, rather than either DNA binding or bacterial mutation being the more valid end point.