ROLE OF MUTAGENESIS IN CARCINOGENESIS

工作概述：大多数化学致癌物诱发DNA损伤

Summary of Work: Most chemical carcinogens induce DNA damage and are mutagenic at specific genetic loci; however, certain carcinogens (including the human carcinogens diethylstilbestrol (DES), asbestos, arsenicals, benzene and testosterone) usually do not induce gene mutations. We examined the ability of these chemicals to induce morphological transformation,gene mutations and chromosome mutations in Syrian hamster embryo (SHE) cells in culture. To examine the ability of estrogens and anti-estrogens to induce cellular transformation and genetic effects, Syrian hamster embryo (SHE) cells were treated with estrogens, 17beta-estradiol (E2) or diethystilbestrol (DES), or with anti-estrogens, tamoxifen (TAM), toremifene (TOR) or ICI 164,384. Treatment with each chemical at 1-30uM for 48 hrs caused morphological transformation of SHE cells in a dose related fashion. The highest frequency was exhibited in SHE cells treated with DES. TOR showed a higher transforming ability when compared to the other anti-estrogens (TAM and ICI 164,348). No significant increases in the frequencies of chromosomal aberrations were observed in SHE cells that were treated with any of the chemicals. However, treatment of SHE cells with each chemical induced a dose-dependent increase of aneuploid cells in the near diploid range. Our results indicate that the ability of the estrogens and anti- estrogens to induce numerical chromosomal abnormality may be involved in their cell transformation activity and potential carcinogenicity. Benzene is a human carcinogen present naturally in petroleum and gasoline. For the simultaneous assessment of benzene-induced carcinogenicity and mutagenicity, benzene and it's principal metabolites, phenol, catechol, and hydroquinone were examined for their ability to induce cell transformation of genotoxic effects using the same mammalian cells in culture. Each of the four compounds induced morphological transformation of Syrian hamster embryo (SHE) cells.