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Genotoxic effects of o-phenylphenol metabolites in CHO-K1 cells
S Tayama1, N Kamiya, Y Nakagawa
1Department of Toxicology, Tokyo Metropolitan Research Laboratory of Public Health, Japan.
Abstract:
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.
Insights
Microsomal activation enhances o-phenylphenol (OPP) genotoxicity, increasing chromosomal aberrations and sister-chromatid exchanges (SCEs) in CHO-K1 cells. This effect correlates with phenylhydroquinone (PHQ) metabolite levels, suggesting PHQ and its oxides are key inducers of these cytogenetic changes.
Area of Science:
- Toxicology
- Genetics
- Cell Biology
Background:
- o-phenylphenol (OPP) is a chemical with potential genotoxic effects.
- Microsomal activation systems, like S9 mix, can alter the toxicity of chemicals.
- Understanding these interactions is crucial for risk assessment.
Purpose of the Study:
- To investigate the role of microsomal activation in OPP-induced genotoxicity.
- To determine the relationship between OPP metabolites and cytogenetic damage.
- To evaluate the effects of phenylhydroquinone (PHQ) and its oxidation products.
Main Methods:
- Cultured Chinese hamster ovary (CHO-K1) cells were exposed to OPP with varying concentrations of S9 mix.
- Chromosomal aberrations and sister-chromatid exchanges (SCEs) were quantified.
- Metabolites, including PHQ, were measured concurrently.
Main Results:
- OPP induced dose-independent chromosomal aberrations and SCEs in the presence of S9 mix.
- The production of PHQ did not increase linearly with higher OPP doses.
- PHQ exhibited cytogenetic effects with or without S9 mix, but was more lethal and oxidized to phenylbenzoquinone (PBQ) without S9.
Conclusions:
- Enhanced cytogenetic effects of OPP with S9 mix correlate with PHQ production.
- PHQ and its further oxidation products (phenylsemiquinone, PBQ) are likely responsible for the observed genotoxicity.
- These findings highlight the importance of metabolic activation in OPP's toxicological profile.