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Species differences in the formation of benzo(a)pyrene-DNA adducts in rodent and human endometrium
Abstract:
The formation of adducts of benzo(a)pyrene metabolites on DNA was investigated in endometrial tissue from humans, hamsters, mice, and rats. anti-Benzo(a)pyrene-7,8-diol-9,10-epoxide was the predominant adduct identified in all the species studied. The amount of (+)-anti-benzo(a)pyrene-7,8-diol-9,10-epoxide bound to DNA from human endometrium was approximately 3 times higher than to DNA from hamster tissue. Among the three animal species examined, the level of this adduct was highest in hamsters and lowest in rats. The high pressure liquid chromatography profiles of adducts formed in endometrium from humans and hamsters were similar, but the specific activity (pmol/mg DNA) of each adduct formed was different. syn-7,8-Dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene adduct was present in humans, hamsters, and rats but was not detected in mouse endometrium. There was an unidentified adduct present only in rat tissue. Rats had the lowest level of total DNA-bound radioactivity and the largest percentage of this total eluted as an uncharacterized radioactive peak that eluted with water (53%). These results demonstrate that endometrial tissues from humans and three rodent species differ with regard to the quantities and proportions of benzo(a)pyrene-DNA adducts formed from benzo(a)pyrene.
Insights
Human and animal endometrial tissues show varying levels of benzo(a)pyrene-DNA adducts. The anti-benzo(a)pyrene-7,8-diol-9,10-epoxide adduct was predominant across species, with significant differences in quantity and proportion.
Area of Science:
- Environmental Toxicology
- Molecular Toxicology
- Carcinogenesis
Background:
- Benzo(a)pyrene is a polycyclic aromatic hydrocarbon found in the environment.
- Metabolites of benzo(a)pyrene can form DNA adducts, potentially leading to mutations.
- Endometrial tissue is a target for various environmental exposures.
Purpose of the Study:
- To investigate and compare the formation of benzo(a)pyrene-DNA adducts in endometrial tissues.
- To identify specific benzo(a)pyrene metabolites that bind to DNA across different species.
- To understand interspecies variations in DNA adduct profiles.
Main Methods:
- Analysis of DNA adducts in endometrial tissue from humans, hamsters, mice, and rats.
- Utilized high-pressure liquid chromatography (HPLC) for adduct profiling.
- Quantified DNA-bound radioactivity and specific adducts.
Main Results:
- The anti-benzo(a)pyrene-7,8-diol-9,10-epoxide was the predominant adduct in all species.
- Human endometrium showed approximately 3 times higher adduct levels than hamster tissue.
- Significant interspecies differences were observed in adduct quantities and proportions, including a unique unidentified adduct in rats.
Conclusions:
- Endometrial tissues exhibit distinct patterns of benzo(a)pyrene-DNA adduct formation.
- Species-specific metabolic activation and detoxification pathways influence adduct levels.
- These findings highlight the importance of considering interspecies variability in toxicological risk assessments.