Premium
Tissue‐specific activities of methylated dibenzo[ c , g ]carbazoles in mice: Carcinogenicity, DNA adduct formation, and CYP1A induction in liver and skin
Author(s) -
TarasValéro Danièle,
PérinRoussel Odette,
Plessis MarieJosé,
Zajdela François,
Périn François
Publication year - 2000
Publication title -
environmental and molecular mutagenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1
H-Index - 87
eISSN - 1098-2280
pISSN - 0893-6692
DOI - 10.1002/(sici)1098-2280(2000)35:2<139::aid-em9>3.0.co;2-6
Subject(s) - carcinogen , adduct , dna , mutagen , dna adduct , chemistry , biology , toxicology , genetics , organic chemistry
The potent multitissue carcinogen 7 H ‐dibenzo[ c , g ]carbazole and nine methylated derivatives, synthesized on the basis of the positions in the parent compound that are involved in metabolism, were tested for their ability to induce sarcomas and hepatic tumors in XVIInc/Z mice. In addition, the capacity of these compounds to induce DNA adducts in skin and liver was investigated by 32 P‐postlabeling analysis after their topical administration. Induction by these compounds of cytochromes P450 of the 1A family in liver and skin was investigated and correlated to their carcinogenic potential. A clear correlation was found between the tissue specificity of DNA binding and the capacity of each compound to induce skin or liver tumors. In contrast, no direct relationship was observed between the capacity of the compounds to induce cytochromes 1A1/1A2 and the tissue specificity of carcinogenesis or DNA binding in liver or skin. The results are discussed with respect to the positions of methyl groups in the 7 H ‐dibenzo[ c , g ]carbazole molecule. Environ. Mol. Mutagen. 35:139–149, 2000 © 2000 Wiley‐Liss, Inc.