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Tumor-initiating activity, mutagenicity, and metabolism of methylated anthracenes
Abstract:
Specific methylated derivatives of anthracene are mutagenic in S. typhimurium and have tumor-initiating activity on mouse skin. In this study, the mutagenic activities of 1-, 2-, and 9-methylanthracene, 2,9- and 9,10-dimethylanthracene, 2,9,-10-trimethylanthracene, 2,3,9,10-tetramethylanthracene, and the photo-oxide of 9,10-dimethylanthracene were determined in S. typhimurium TA98 and TA100. The relative tumor-initiating activities of these compounds were also evaluated. These bioassays indicate that increased mutagenic potency and tumor-initiating activity are associated with the presence of a methyl substituent at both the 9- and 10- position of anthracene. Metabolism studies suggest that the biological activity of specific methylated anthracenes may be related to the formation of a simple epoxide adjacent to a peri-methyl substituent.
Insights
Methylated anthracene derivatives show mutagenic and tumor-initiating activity. Increased activity is linked to methyl groups at the 9- and 10- positions of anthracene, potentially due to epoxide formation.
Area of Science:
- Environmental Chemistry
- Toxicology
- Organic Chemistry
Background:
- Methylated anthracene derivatives are known mutagens and tumor initiators.
- Understanding structure-activity relationships is crucial for risk assessment.
Purpose of the Study:
- To evaluate the mutagenic and tumor-initiating activities of various methylated anthracenes.
- To correlate structural features with biological potency.
Main Methods:
- Bacterial mutagenicity assays using S. typhimurium strains TA98 and TA100.
- In vivo tumor-initiation bioassays on mouse skin.
- Metabolism studies to investigate biological activity mechanisms.
Main Results:
- Mutagenic and tumor-initiating activities varied among methylated anthracenes.
- Compounds with methyl groups at the 9- and 10- positions exhibited higher potency.
- Metabolism studies suggested epoxide formation adjacent to peri-methyl substituents.
Conclusions:
- The 9- and 10- positions of anthracene are critical for methyl-induced mutagenicity and tumor initiation.
- Epoxide formation adjacent to methyl groups may mediate the biological activity of methylated anthracenes.