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

S. C. Booth, H. Bösenberg, R. C. Garner, P. J. Hertzog, K. Norpoth

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Abstract

The activation of aflatoxin B1 (AFB1) has been compared in two in vitro systems: (1) binding to DNA in liver slices incubated with [14C] or [3H]AFB1; (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 G1 (AFG1) compared with AFB1. The results from DNA binding in liver slices showed the following trends: rat > hamster > mouse, control > phenobarbitone-pretreated rat and AFB1 > AFG1 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 AFB1 carcinogenesis. This result suggests that sex differences in AFB1 carcinogenicity may be due to differences in repair of lesions or during the promotion phase of carcinogenesis. The levels of binding of [3H]AFB1 to DNA slices from fresh human liver biopsies showed considerable variation between the six samples. Values ranged from 0.7-8.5 ng AFB1/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, AFB1 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.

Original languageEnglish
Pages (from-to)1063-1068
Number of pages6
JournalCarcinogenesis
Volume2
Issue number10
DOIs
Publication statusPublished - 1 Dec 1981
Externally publishedYes

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