This proposal deals with the use of ESR in spin-labelling and spin trapping studies of possible free radicals involved in the initiation and/or promotion phase of carcinogenesis. Studies are directed to free radicals produced in the decomposition of the nitroroamine and amides. Mutagenesis assays are developed to study the effects of these free radicals in the Ames tester system. Spin-labelling, reconstitution, melting and digestion studies have been designed to probe the interaction between activated carcinogens and active and inactive chromatin at nucleosomal level. Studies on the role of the HMG proteins in defining active chromatin are described. Spin-labelling and spin-trapping studies have also been designed to probe the effect of structural conformational changes on reconstituted cytochrome P-450 mixed function oxidase substrate specificity.
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