DESCRIPTION: (Adapted for applicant's abstract) Based on the fact that lead toxicity is a significant human health problem, this proposal has been designed to examine the genetic basis for inter-individual susceptibility/resistance to the toxicological effects of lead. While multiple factors can and do affect the potential toxicity to lead exposure, clear epidemiological data link certain genotypes to different clinical outcomes resulting from lead exposure. The experimental approach will use Drosophila melanogaster as the test organism because of the rich genetic knowledge associated with this organism, ease of manipulation at the molecular level, availability of a wide variety of strains and mutants, and documented relevance in many cases to higher organisms. Specifically, two general aims are contemplated to lead to the identification and characterization of gene(s) responsible for tolerance to lead: (a) by isolating a lead resistance allele already uncovered on the X chromosome;and (b) by isolating additional genetic modifiers of lead tolerant phenotypes. Traditional classical genetics and modern molecular genetics tools will be used to achieve these aims. With the gene(s) isolated for Drosophila, searches of human cDNA libraries will be performed to isolate related, analogous or homologous human genes.