Two-stage skin carcinogenesis in sensitive and resistant mouse strains

Area of Science:

• Carcinogenesis research
• Toxicology and pharmacology
• Genetics and animal models

Background:

• Laboratory mouse strains exhibit significant variations in susceptibility to chemical carcinogenesis.
• Two-stage skin carcinogenesis models utilize initiators like 7,12-dimethylbenz[a]anthracene (DMBA) and promoters such as croton oil.
• Understanding strain-specific responses is crucial for elucidating carcinogenic mechanisms.

Purpose of the Study:

• To clarify the underlying basis for strain-dependent differences in susceptibility to two-stage skin carcinogenesis.
• To investigate the roles of DMBA as both initiator and potential promoter in susceptible (LACA) and resistant (BALB/c) mouse strains.
• To evaluate the contribution of promoter metabolism to observed strain differences.

Main Methods:

• Comparative analysis of two-stage skin carcinogenesis using DMBA (initiator) and croton oil (promoter) in LACA and BALB/c mice.
• Dose-response studies with DMBA to assess its efficacy as a complete carcinogen and in two-stage protocols.
• Experiments involving altered croton oil application and substitution with anthralin to assess promoter activity and degradation.

Main Results:

• DMBA demonstrated greater efficacy as a complete carcinogen in LACA mice compared to BALB/c mice.
• Dose-response data suggested that DMBA's metabolic activation was not the limiting factor for resistance in BALB/c mice.
• Strain differences in susceptibility were not attributed to variations in croton oil or anthralin promoter degradation.

Conclusions:

• Strain differences in response to DMBA in both one- and two-stage carcinogenesis may stem from DMBA's dual role as an initiator and promoter.
• The capacity of mouse strains to repair DMBA-induced DNA damage remains a potential factor influencing susceptibility.
• Differences in promoter metabolism do not appear to account for the observed strain-specific variations in skin carcinogenesis.