In vivo carcinogenesis studies have shown that the SENCAR mouse is unusually susceptible to skin carcinogenesis by initiation and promotion. This sensitivity is not a result of differences in carcinogen metabolism between SENCAR and more resistant mouse strains; and grafting experiments show that the enhanced sensitivity is a property of the skin itself, suggesting the usefulness of in vitro studies to elucidate the mechanism. Such studies have shown that cultured epidermal cells of SENCAR and the more resistant Balb/c strain are remarkably similar in a variety of respects, including DNA repair, binding and metabolism of epidermal growth factor, immunological properties, and growth kinetics in response to modulation of carcinogenesis. Recent results of in vitro experiments with foci of cells resistant to CA2+-induced terminal differentiation following carcinogen treatment suggest that the number of initiated cells induced in SENCAR and Balb/c are equal but that there are qualitative differences in the nature of the initiated cells. Evidence points to enhanced sensitivity to promotion as an important aspect of SENCAR susceptibility. In vivo carcinogenesis studies demonstrate a different papilloma response between SENCAR and CD-1 mice. In CD-1 mice, papilloma incidence continues to rise with continued TPA treatment, while in SENCAR papilloma regression occurs whether or not TPA is continued. Both in vivo and in vitro data support the existence of a constitutively initiated cell population in SENCAR mouse skin but not skin of more resistant strains. The contribution of such cells to SENCAR susceptibility has not been defined.

Agency
National Institute of Health (NIH)
Institute
Division of Cancer Epidemiology And Genetics (NCI)
Type
Intramural Research (Z01)
Project #
1Z01CP005178-05
Application #
4692328
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
5
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Cancer Epidemiology and Genetics
Department
Type
DUNS #
City
State
Country
United States
Zip Code