The long range goal of this project is to explore the toxicological importance of aliphatic epoxides in the metabolism of alkene compounds as well as to study the genotoxicity of these epoxides in their role as laboratory and industrial reagents. In support of this goal it is proposed to continue to study structure-mutagenicity relationships for such epoxides and attempt to develop equations for quantitative structure-activity relationships that would describe the mutagenicity of series of related epoxides. Compounds of interest are (a) polycyclic aromatic alkyl epoxides; (b) styrene oxide derivatives (c) diol epoxides and (d) epoxides related to fecapentaene. These compounds will be tested for mutagenicity with the Ames Salmonella and with mouse lymphocyte culture systems. The base-pair changes upon mutation will be followed by the use of the Salmonella strains designed for that purpose. The epoxides will also followed for their rates of detoxication by the Ames tests, mouse lymphocyte cultures and HPLC in the presence of liver-enzyme systems. The use of lymphocyte cultures from mice treated with epoxides will be evaluated to replace the present use bone-marrow genotoxicity as a method of following in vivo epoxide toxicity. Gene-mutation assays in mice will also be conducted as will be in vivo adduct studies using 32P postlabeling. The purpose being to relate in vivo toxicity to in vitro testing for epoxides.
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