DNA DAMAGE, PROMOTION AND THE PROOXIDANT STATE

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A research project is proposed for investigating the role of prooxidant states in the cell on the carcinogenesis process. The investigation would entail the identification, isolation and characterization of lesions from DNA oligomers that are associated with the effects of reactive oxygen species. These lesions will be sought also in the DNA of cells exposed in culture to prooxidant conditions. The cells to be employed in the investigation are epidermal cells of "normal" and "initiated" lines which respond differently to promotion. Conditions and agents which may lead to the generation of reactive oxygen species, such as autoxidizing agents (e.g. ascorbic acid) or phorbol esters (e.g. PMA) will be investigated for their ability to promote transformation. The study is designed to test the hypothesis that promoting agents affect carcinogenesis by a modification of the genome.