6533b831fe1ef96bd1298443

RESEARCH PRODUCT

Fjord-region diol-epoxides of benzo[c]chrysene are potent inducers of micronuclei in murine bone marrow

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Abstract Vicinal diol-epoxides are the best established carcinogenic metabolites of polycyclic aromatic hydrocarbons. Numerous studies have demonstrated their high genotoxic activity in various in vitro test systems. However, in vivo mutagenicity data are not available. The fjor-region diol-epoxides of benzo[ c ]chrysene combine high mutagenic activity in vitro with hydrolytic stability. They were tested for the induction of micronuclei in the bone marrow following intraperitoneal administration to NMRI mice. The anti diasteromer of the diol-epixode enhanced the frequency of micronucleated polycrhomatic erythrocytes strongly (7–19-fold above the value in untreated controls) over a very wide dose range (2.5–300 μmol/kg body weight). The syn diastereomer demonstrated similar effects, but required about 5 times higher doses. The corresponding proximate mutagen, benzo[ c ]chrysene- trans -9,10-dihydrodiol, was only moderately active, whereas the positive control substance, benzo[ a ]pyrene- trans -7,8-dihydrodiol, was strongly active. The study indicates that intraperitoneally administered diol-epoxides of benzo[ c ]chrysene may reach the bone marrow. Therefore, it will be possible to study the influence of metabolic modulation, e.g. by enzyme induction, on the effects of these ultimate mutagens and their metabolic precursors in vivo.