The basic objective of our research project is to gain information about the mechanisms of radiation carcinogenesis induced by x-rays or UV light in in vitro assay systems. We will investigate interactions between radiation and chemical agents in the induction of malignant transformation in vitro. The specific chemical agents we are studying have known interactive effects on carcinogenesis in vivo, and have been observed to enhance or suppress the expression of the malignant phenotype in vitro. Studies on the mechanisms involved in the induction of radiation transformation and its modification by chemical agents in an in vitro system, in which cellular proliferation and other environmental conditions can be precisely controlled, should yield more information about the mechanisms involved in radiation induced cancer. Specifically, during the present grant period we will attempt to determine whether the following phenomena are involved in radiation transformation in vitro and its modification by chemical agents: DNA recombinational events, free radical intermediates, cell growth modification, patterns of cellular differentiation, and the induction of specific proteases. In addition, we will study interactions between agents that inhibit radiation transformation in vitro. We will continue to use the 10T1/2 mouse embryo cell line for most of the proposed experiments involving transformation though we propose to develop a human diploid cell transformation system to study in parallel with the mouse cells.
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