Benzene-, catechol-, hydroquinone- and phenol-induced cell transformation, gene mutations, chromosome aberrations, aneuploidy, sister chromatid exchanges and unscheduled DNA synthesis in Syrian hamster embryo cells.
Benzene is a human carcinogen present naturally in petroleum and gasoline. For the simultaneous assessment of benzene-induced carcinogenicity and mutagenicity, benzene and its principal metabolites, phenol, catechol and hydroquinone were examined for their ability to induce cell transformation and genotoxic effects using the same mammalian cells in culture. Each of the four compounds induced morphological transformation of Syrian hamster embryo (SHE) cells. Catechol was the most potent, inducing transformation at concentrations of 1-30 microM, followed by hydroquinone (3-30 microM), phenol (10-100 microM) and benzene (only at 100 microM). Gene mutations at two loci in SHE cells were induced by all four compounds, with catechol being the most potent; both ouabain-resistant and 6-thioguanine-resistant mutant frequencies were increased. Chromosomal aberrations in SHE cells were especially induced by catechol, lesser by hydroquinone, and to a marginal extent by phenol at only the 100 microM concentration, whereas sister chromatid exchanges in SHE cells occurred with hydroquinone (1-30 microM), catechol (10-30 microM) and phenol (1000-3000 microM). Aneuploidy in the near diploid range of SHE cells was significantly induced by benzene and catechol. All three metabolites induced unscheduled DNA synthesis in SHE cells, whereas benzene did not. This is the first report that the cell transforming activity and mutagenicity of benzene and its metabolites were assessed with the same mammalian cells in culture. The results provide evidence that benzene and several of its metabolites are cell transforming and genotoxic to cultured mammalian cells.
Tsutsui
T
T
Department of Pharmacology, School of Dentistry at Tokyo, Nippon Dental University, Japan.
Hayashi
N
N
Maizumi
H
H
Huff
J
J
Barrett
J C
JC
D000782:Aneuploidy; D000818:Animals; D001554:Benzene / Q000494:pharmacology*; D002273:Carcinogens / Q000494:pharmacology*; D002396:Catechols / Q000494:pharmacology*; D002478:Cells, Cultured; D002869:Chromosome Aberrations; D006224:Cricetinae; D004247:DNA / Q000096:biosynthesis*; D006873:Hydroquinones / Q000494:pharmacology*; D016296:Mutagenesis / Q000187:drug effects*; D010042:Ouabain / Q000378:metabolism; D019800:Phenol; D010636:Phenols / Q000494:pharmacology*; D015203:Reproducibility of Results; D012854:Sister Chromatid Exchange / Q000187:drug effects*; D013565:Sympatholytics / Q000494:pharmacology*; D013866:Thioguanine / Q000378:metabolism; D014170:Transformation, Genetic / Q000187:drug effects*
D002273:Carcinogens; D002396:Catechols; D006873:Hydroquinones; D010636:Phenols; D013565:Sympatholytics; D019800:Phenol; D010042:Ouabain; D004247:DNA; D013866:Thioguanine; D001554:Benzene