Mutation induction by rodent liver microsomal metabolites of aflatoxins B1 and G1 in Neurospora crassa

Matzinger, Peter K.; Ong, Tong-man

doi:10.1016/0027-5107(76)90053-1

Cited by 17 publications

(1 citation statement)

References 12 publications

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“…In V79 cells, this effect was more pronounced than in human lymphocytes. These results are consistent with earlier observations in human lymphocytes [Vijayalaxmi et al, 1979;Iskandar and Vijayalaxmi, 1981;Inoue et al, 19831, and CHO and DON cells Baker et al, 1983;Vijayalaxmi et al, 19791. In non-mammah 'an cells (yeasts and bacteria), AFBl was not mutagenic without external activation [Matzinger and Ong, 1976;Callen et al, 1977;Suit et al, 19771. This indicates that mammalian cells have some internal metabolic capacity for AFB 1 activation.…”

Section: Discussionmentioning

confidence: 99%

Comparison of S9 mix and hepatocytes as external metabolizing systems in Mammalian cell cultures: Cytogenetic effects of 7,12‐dimethylbenzanthracene and aflatoxin B1

et al. 1986

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Two external metabolizing systems, S9 mix from Aroclor-induced rat livers and freshly isolated hepatocytes, were used for activation in cultures of human lymphocytes and V79 cells. 7, 12-dimethylbenzanthracene (DMBA) and aflatoxin B1 (AFB1) were employed as indirectly acting reference mutagens. Mutagenic effects were measured by induction of sister chromatid exchange (SCE). With DMBA, SCE-inducing effects were found to be quite similar after activation by S9 mix and activation by hepatocytes. In human lymphocytes nearly the same dose-effect relationships were found with both metabolizing systems; in V79 cells the hepatocyte-mediated induction of SCE was detectable at slightly lower concentrations than the S9-mediated SCE induction. In contrast with AFB1, S9 activation led to a stronger SCE induction than hepatocyte activation in both target cells. The induction of chromosomal aberrations by AFB1 after activation by the two metabolizing systems was also analysed in V79 cells. This experiment again revealed that AFB1 was more efficiently activated by S9 mix than by hepatocytes, and it appeared that AFB1 is a more potent inducer of chromosomal aberrations than of SCE. The different activation capacities of the two metabolizing systems for AFB1 may be due to the maintenance of inactivation mechanisms in hepatocytes or to the Aroclor induction of the S9 fraction. Our experiments have shown that the suitability of hepatocytes as an activation system is not restricted to microbial or eukaryotic point mutation assays, but that hepatocyte metabolism can also be successfully included in cytogenetic tests with short- and long-term cultures of mammalian target cells.

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Section: Discussionmentioning

confidence: 99%

Comparison of S9 mix and hepatocytes as external metabolizing systems in Mammalian cell cultures: Cytogenetic effects of 7,12‐dimethylbenzanthracene and aflatoxin B1

et al. 1986

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Species differences in mutagenicity testing: I. Micronucleus and SCE tests in rats, mice, and Chinese hamsters with aflatoxin B1

Madle

Korte

Beek

1986

Teratog Carcinog Mutagen

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Three animal species used in in vivo mutagenicity testing--rats, mice and Chinese hamsters--were compared with respect to their mutagenic response to the mycotoxin aflatoxin B1 (AFB1). The micronucleus test and the SCE test with bone marrow cells were chosen as test methods, employing similar protocols for all species. The mutagenic potential of AFB1 was detected with rats and mice but not with Chinese hamsters. Rats were more susceptible to the mutagenic action of AFB1 than mice with regard to the effective dose. A difference in sensitivity between males and females was evident in rats and mice: male animals exhibited higher induced micronucleus frequencies than females, and a clear SCE-inducing effect was only detectable in male animals. These results are in agreement with those of in vitro and carcinogenicity studies. They may be due to metabolic differences between the species and sexes, predominantly differences in glutathione conjugation of the reactive AFB1 epoxide and in the formation of the metabolite aflatoxicol. Furthermore, it could be demonstrated that AFB1 seems to be a more potent inducer of micronuclei than of SCE. Since our results obtained with rats and mice were clearly positive, but with the Chinese hamster the mutagenic potential of AFB1 was not detectable with the test systems used, it can be concluded that the choice of an "inappropriate" test species may lead to a false negative judgment on the genotoxic potential of a test compound.

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Comparative Mutagenicity of Aflatoxin Bl and Vinyl Chloride

Kilbey

1981

Comparative Chemical Mutagenesis

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Mutation induction by rodent liver microsomal metabolites of aflatoxins B1 and G1 in Neurospora crassa

Cited by 17 publications

References 12 publications

Comparison of S9 mix and hepatocytes as external metabolizing systems in Mammalian cell cultures: Cytogenetic effects of 7,12‐dimethylbenzanthracene and aflatoxin B1

Comparison of S9 mix and hepatocytes as external metabolizing systems in Mammalian cell cultures: Cytogenetic effects of 7,12‐dimethylbenzanthracene and aflatoxin B1

Species differences in mutagenicity testing: I. Micronucleus and SCE tests in rats, mice, and Chinese hamsters with aflatoxin B1

Comparative Mutagenicity of Aflatoxin Bl and Vinyl Chloride

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