It is generally accepted that the genetic background is a determining factor in the response of individuals to environmental carcinogens and the importance of genetic factors in chemical carcinogens has been well established in several animal models. In the mouse skin carcinogenesis system, studies from different laboratories have shown that genetic susceptibility affects the initiation and promotion phases of carcinogenesis. Based on recent preliminary results from our laboratory, we postulate that tumor progression in the mouse skin model (i.e., the ability of papillomas to develop premalignant changes and convert to squamous cell carcinomas) is genetically regulated by modifier genes which are independent of the genes conferring susceptibility to tumor promotion. The long term objective of this project is to establish a genetic model for the susceptibility to tumor progression in the mouse skin and to identify the putative progression susceptibility genes.
The specific aims of this proposal are: 1) To establish a genetic model of tumor progression susceptibility using F1,F2 between SENCAR derived mouse strains. 2) To map tumor progression susceptibility genes, using the F2 and backcrosses of specific aim 1 and microsatellite markers. 3) To investigate phenotypic differences between SSIN and SENCAR B/pt that can provide clues for the differential progression of the papilloma.
