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.