Site and lack of strict copy number control. The approach outlined in this study provides a powerful alternative for comparative transgenic analysis where the functional consequences of transgene variation can be assessed within a stable chromosomal context. The stem cells generated within the study can, in the future, be used for the generation of mouse models to assess the comparative strengths of these promoters in vivo and to determine whether the various promoters are equally active in all cell types. Cytochrome P450s have long been of particular interest because they are critical for the detoxification and/or activation of xenobiotics such as drugs, pesticides, plant toxins, chemical carcinogens and mutagens. They are also involved in metabolizing endogenous compounds such as hormones, fatty acids, and steroids. Basal and up-regulation of P450 gene expression can significantly affect the disposition of xenobiotics or endogenous compounds in the tissues of organisms and thus alter their pharmacological/toxicological effects. Insect cytochrome P450s are known to play an important role in detoxifying exogenous compounds such as insecticides and plant toxins. A significant characteristic of insect P450s associated with the enhanced metabolic detoxification of insecticides is the increase in the levels of P450 proteins and P450 activity that results from constitutive AG-013736 overexpression of P450 genes in insecticide resistant insects, which has been implicated in the development of resistance to insecticides and tolerance to plant toxins. Another feature of some insect P450 genes is that their expression can be induced by both exogenous and endogenous compounds, a phenomenon known as induction. It has been suggested that the induction of P450s and their activities in insects is involved in the adaptation of insects to their environment and, hence, the development of insecticide resistance. While all insects probably possess some capacity to detoxify insecticides and xenobiotics, the degree to which they can metabolize and detoxify these toxic chemicals is of considerable importance to their survival in a chemically unfriendly environment and to the development of resistance. The constitutively increased expression and induction of P450s are both thought to arise in response to increased levels of detoxification of insecticides. It has been suggested that many chemical inducers act as substrates for P450s and that the induction or modulation of P450s by such substrates will, in turn, reduce the effects of the substrates by enhancing.