Genotoxic effects of o-phenylphenol metabolites in CHO-K1 cells.
The effects of microsomal activation and/or deactivation on the induction of chromosomal aberrations and sister-chromatid exchanges (SCEs) in cultured Chinese hamster ovary cells (CHO-K1 cells) by o-phenylphenol (OPP) were studied, and concurrently the metabolites were determined. After a 3-h incubation in the presence of 15% S9 mix (45 microliters/ml of S9), OPP (25-150 micrograms/ml) dose-independent SCEs and chromosomal aberrations were induced, while the amount of phenylhydroquinone (PHQ) metabolite produced from OPP did not increase linearly in the higher doses. The maximum induction of chromosomal aberrations was 18% at the 150 micrograms/ml dose, and of SCEs 13.8/cell at 75 micrograms/ml. The corresponding control values were 3% and 5.8/cell. The lowest dose required to induce SCEs in the presence of S9 mix was 25 micrograms/ml. Changing the percent of S9 mix (0-50%) while holding the OPP dose constant (100 micrograms/ml) produced a correlation between SCEs and the production of PHQ. PHQ caused cytogenetic effects both with and without S9 mix, however, in the absence of S9 mix it was more lethal and was oxidized to phenylbenzoquinone (PBQ). These results suggest that the enhanced cytogenetic effects of OPP by the addition of S9 mix correlated with the amount of PHQ produced or with the further oxides of PHQ such as phenylsemiquinone and/or PBQ which are capable of being produced from PHQ spontaneously or by the mixed-function oxidase system.
Tayama
S
S
Department of Toxicology, Tokyo Metropolitan Research Laboratory of Public Health, Japan.
Kamiya
N
N
Nakagawa
Y
Y
D000818:Animals; D001711:Biotransformation; D001713:Biphenyl Compounds / Q000633:toxicity*; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid; D002869:Chromosome Aberrations; D006224:Cricetinae; D003412:Cricetulus; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D008862:Microsomes, Liver / Q000378:metabolism; D008938:Mitosis / Q000187:drug effects; D012854:Sister Chromatid Exchange / Q000187:drug effects; D013997:Time Factors
D001713:Biphenyl Compounds; C004369:2-phenylphenol