Xenobiotic-metabolizing enzymes play a crucial role in the ability of insects to survive in toxic environments. The aims of this research proposal are to provide a better insight on the developmental and physiological factors influencing the insect (cytochrome P450) polisubstrate monooxygenases. A better understanding of these factors may generate useful strategies in the control of insects of medical and economic importance. The mosquito Culex pipiens (a vector of togaviruses in North America) and the cockroach Diploptera punctata will be used. Developmental changes in polysubstrate monooxygenases will be studied. The functional components, cytochrome P450 and NADPH-cytochrome c reductase, as well as several monooxygenase activities will be characterized in biochemically defined subcellular fractions of several tissues taken at precise developmental stages. In the adult stage of these two species, trophic factors will be dissociated from ontogenetic factors. The hypothesis that the developmental program of polysubstrate monooxygenase changes is implemented through variations in hormonal titers will be tested. The induction of polysubstrate monooxygenases by xenobiotics and by hormones will be compared in larval and adult stages to reveal possible quantitative or qualitative changes in these enzymes. Ontogenetic changes in polysubstrate monooxygenases and other xenobiotic-metabolizing enzymes will be related to changes in insecticide tolerance and to changes in ecological conditions.