The versatility of the Ames Salmonella tester strains for detection and mutagens and protential carcinogens will be extended with two major objectives in mind: (1) increased sensitivity for single chemical classes of mutagens or broadened range of mutagen detection, and (2) application of existing and newly derived strains to pinpoint specific classes of mutagens and antimutagens that are often present in complex mixtures. Under the latter category we seek strains with unique, or at least greatly narrowed, but highly sensitive responsiveness to particular chemical classes of mutagens and antimutagens. Direct-selection procedures will be used to procure mutants defective and mutants derepressed for bacterial glutathione S-transferase activity and in glutathione biosynthesis. Strains defective in transalkylase repair of methyl- and ethyl-06 guanosyl residues will be procured in the hisG46 background that carries a GGG/CCC missense triplet. We will attempt to isolate a second-step mutant even more sensitive to alkylation mutagenesis and defective in 02 alkyl-cytosine excision repair. We also will investigate two different Salmonella strains, already in hand, that have exhibited increased sensitivities to mutagenesis by particular frameshift mutagens in preliminary tests. Procurement and analyses of the proposed new mutants and some in stock should assist in unravelling critical defense mechaisms against electrophilic chemicals and free radicals that precede actual DNA damage. For example how important is cellular content, per se, of glutathione, of polyamines, of L-histidine and L-carnosine in cellular defense against electrophiles and singlet oxygen? Some of the mutants also will be valuable in pinpointing the nature of DNA lesions that are responsible for mutagenesis in vivo. Improved Salmonella strains amenable to more diverse types of mutagen anti-mutagen testing than now possible should find ready and widewpread adoption because related strains already are in wide use both by testing laboratories and by molecular biologists/geneticists. One key to cancer prevention is the detection and elimination of dangerous mutagens from man's environment prior to extensive human exposure. A second key is the detection and quantification of naturally occurring antimutagens of biological importance; only a few of the latter have been well-characterized to date.
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