The objective of this line of research is to understand some of the factors which are responsible for the removal of deoxyribonucleoside-adducts from DNA. In this regard, we will determine the effects of benzo(a)pyrene (BP) upon the alkaline elution profile of a cloned hamster tracheal cell line. We will determine the nature of the adducts; their biological stability as altered by vitamin A analogs and chronic administration of BP; their occurrence in micrococcal nuclease sensitive- and -resistant portions of the tracheal chromatin. The effects of asbestos (crocidolite) upon these parameters will be measured and the ability of the vitamin A analogs to prevent any asbestos effects will be pursued. Finally, we will continue studies on the purification of the enzyme system present in rat liver which is responsible for the removal of O6-methylguanine from methylated DNA (after methylnitrourea). We will initiate studies in the repair enzymes involved in the removal of deoxyguanosine-BP and deoxyadenosine-BT adducts from DNA alkylated with the diol epoxides of BP. We will employ liver and tracheal extracts.
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