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Comparison of benzo[a]pyrene-DNA adduct levels in mouse and rat epidermis and dermis
Abstract:
Male Swiss mice and Wistar rats were treated topically with 250 nmol/mouse and 750 nmol/rat of [3H]benzo[a]pyrene ([3H]BaP). The initial level of total BaP--DNA and the individual modified deoxyribonucleoside adducts were similar in the skin epidermis of the two species. The concentration of these adducts was approximately 3 times less in both mouse and rat dermis. The decreased amount of BaP bound to DNA of mouse dermis may be related to the resistance of this tissue to the carcinogenic action of BaP. The ability of both the mouse (susceptible) and rat (resistant) skin to form BaP-bound products similar in nature and ratio in the epidermal and dermal DNA, suggests that other mechanisms are involved in the difference in the biological response of epidermis versus dermis to the carcinogenic effect of BaP.
Insights
Benzo[a]pyrene (BaP) DNA adducts were similar in mouse and rat skin epidermis but lower in dermis. Mouse dermal resistance to BaP carcinogenicity may involve mechanisms beyond adduct levels.
Area of Science:
- Toxicology
- Carcinogenesis
- Biochemistry
Background:
- Benzo[a]pyrene (BaP) is a polycyclic aromatic hydrocarbon and a known carcinogen.
- Understanding differential tissue susceptibility to carcinogens is crucial for risk assessment.
Purpose of the Study:
- To compare the formation and distribution of BaP-DNA adducts in the skin of mice and rats.
- To investigate potential mechanisms underlying differential susceptibility to BaP carcinogenicity in skin tissues.
Main Methods:
- Topical application of radiolabeled [3H]benzo[a]pyrene ([3H]BaP) to male Swiss mice and Wistar rats.
- Quantification of total BaP-DNA and individual modified deoxyribonucleoside adducts in epidermal and dermal DNA.
Main Results:
- Initial levels of BaP-DNA adducts were comparable in the epidermis of both species.
- Adduct concentrations were approximately three times lower in the dermis of both mice and rats.
- Lower BaP-DNA adduct levels in mouse dermis may correlate with its resistance to BaP-induced carcinogenesis.
Conclusions:
- While BaP-DNA adduct formation is similar in mouse and rat epidermis, dermal levels are significantly lower.
- The similar adduct profiles in epidermis and dermis suggest that factors other than adduct quantity influence differential biological responses to BaP.