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Mutation in mammalian cells by isomers of 5-methylchrysene diolepoxide
Abstract:
The two pairs of diastereomeric anti- and syn-diolepoxide derivatives of 5-methylchrysene in both bay regions were tested for cytotoxicity and for mutagenicity at the hprt locus of chinese hamster V79 cells as determined by the ability of the cells to form colonies in medium containing 6-thioguanine. The concentration of compound in the cell media required to achieve 37% survival ranged from 0.3 to 4.5 micrograms/ml. Although the mutagenic effectiveness, i.e. the induced mutation frequency per unit concentration of compounds, varied over a 30-fold range, the mutagenic efficiency, i.e. the induced mutation frequency at an equivalent level of cell survival, showed only a 3-fold variation. The anti-1,2-diol-3,4-epoxide isomer (anti-5MCDE-I) was found to be the most mutagenic of the 5-methylchrysene diolepoxide isomers. This finding is consistent with previous observations on the tumorigenicity of these diolepoxides.
Insights
The anti-1,2-diol-3,4-epoxide isomer of 5-methylchrysene was the most mutagenic diolepoxide derivative tested. This finding aligns with prior research on the tumorigenicity of these compounds.
Area of Science:
- Chemical carcinogenesis
- Toxicology
- Molecular biology
Background:
- Polycyclic aromatic hydrocarbons (PAHs) are environmental pollutants.
- Metabolism of PAHs can produce reactive intermediates, such as diolepoxides.
- These metabolites are implicated in DNA damage and cancer initiation.
Purpose of the Study:
- To assess the cytotoxicity and mutagenicity of 5-methylchrysene diolepoxide derivatives.
- To compare the mutagenic effectiveness and efficiency of different isomers.
- To correlate mutagenicity with known tumorigenicity data.
Main Methods:
- Chinese hamster V79 cells were exposed to varying concentrations of 5-methylchrysene diolepoxide isomers.
- Cytotoxicity was determined by colony formation in medium containing 6-thioguanine.
- Mutagenicity was assessed by measuring induced mutation frequency at the hprt locus.
Main Results:
- Cytotoxicity varied, with concentrations for 37% survival ranging from 0.3 to 4.5 µg/ml.
- Mutagenic effectiveness showed a 30-fold variation, while mutagenic efficiency had a 3-fold variation.
- The anti-1,2-diol-3,4-epoxide isomer (anti-5MCDE-I) exhibited the highest mutagenicity.
Conclusions:
- The anti-5MCDE-I isomer is the most potent mutagen among the tested 5-methylchrysene diolepoxides.
- Mutagenic efficiency provides a more consistent measure of genotoxicity across different compounds.
- Results support the link between specific diolepoxide structures and carcinogenic potential.