Related Experiment Videos
Benzo[a]pyrene diol epoxide I modification of DNA in human skin xenografts
1Department of Physiological Chemistry, Ohio State University, Columbus 43210.
Abstract:
Human skin xenografts were established on the subscapular area of skin of nude (nu/nu NIH-Swiss background) mice. When treated with benzo[a]pyrene diol epoxide I (BPDE I), specific carcinogen-DNA adducts were formed. Separation and identification of these adducts by the 32P-postlabeling technique indicated that the 7R- and 7S-BPDE I-dpGp adducts were the major adducts. Xenografts pretreated with either allantoin or anthralin showed an increase in the major 7R- and 7S-BPDE I adducts compared to only BPDE I treatment. Likewise, we observed an increase in the quantity of different minor adducts. The ratios between the minor and major adducts in the pretreated grafts remained consistent with the ratio in the grafts treated with BPDE I only. We conclude that these modulators induce cells in the xenograft to enter S phase of the cell cycle. Moreover, we observed that these compounds altered the quantity of the minor carcinogen-DNA adducts without altering the overall ratios between the major 7R- and 7S-BPDE I-dpGp adducts and the minor carcinogen-DNA adducts.
Insights
Allantoin and anthralin increase major and minor carcinogen-DNA adducts in human skin xenografts. These compounds also induce S phase cell cycle entry without altering adduct ratios.
Area of Science:
- Toxicology
- Carcinogenesis
- Dermatology
Background:
- Human skin xenografts on nude mice provide a model for studying carcinogen-DNA adduct formation.
- Benzo[a]pyrene diol epoxide I (BPDE I) is a specific carcinogen that forms DNA adducts.
- Understanding adduct formation is crucial for assessing carcinogenic risk.
Purpose of the Study:
- To investigate the effect of allantoin and anthralin pretreatment on BPDE I-induced DNA adducts in human skin xenografts.
- To determine if these modulators alter the types or ratios of carcinogen-DNA adducts.
- To explore the impact of these compounds on cell cycle progression.
Main Methods:
- Establishment of human skin xenografts on nude mice.
- Treatment with BPDE I, allantoin, or anthralin.
- Separation and identification of carcinogen-DNA adducts using the 32P-postlabeling technique.
Main Results:
- BPDE I treatment formed major 7R- and 7S-BPDE I-dpGp adducts.
- Pretreatment with allantoin or anthralin increased both major and minor BPDE I-DNA adducts.
- The ratios of minor to major adducts remained consistent across treatment groups.
- These modulators induced xenograft cells to enter S phase.
Conclusions:
- Allantoin and anthralin enhance the formation of specific BPDE I-DNA adducts.
- These compounds promote cell cycle progression into S phase.
- The modulation of adducts occurs without altering the overall adduct profile ratios.