Comparisons of the regulation of expression of insect and mammalian cytochrome P450 monooxygenases (P450s) provide potential insight into the patterns of detoxification of environmental toxins. The biochemical response to environmental toxins may be similar between insects and mammals in that they share the molecular machinery, including DNA elements and transcription factors, common to the regulatory networks for detoxification genes. In insects, P450s detoxify a variety of fat-soluble toxins, including natural plant compounds and environmental pollutants. Among these, the CYP6B1 and CYP6B3 proteins of the black swallowtail butterfly Papilio polyxenes participate in the metabolism of toxic xanthotoxin and their transcripts are induced 5-fold by dietary exposure to this compound. Parallel dietary exposure to benzo[a]pyrene, an environmental pollutant, does not induce metabolism of xanthotoxin to any extent. Analysis of the CYP6B1 and CYP6B3 promoters indicates that basal and xanthotoxin-inducible expression of these genes are regulated by novel xanthotoxin-response elements and, possibly, by aryl hydrocarbon and antioxidant response elements that have counterparts in vertebrate systems. Specific nucleotides within these latter elements that are critical for differential regulation by aryl hydrocarbons and antioxidants are conserved between the insect CYP6B1 and CYP6B3 and the murine CYP1A1 genes. Sf9 cell transfection assays conducted with CYP6B1 promoter: CAT fusion constructs indicate that the xanthotoxin response element by itself is not sufficient for xanthotoxin-inducible expression and that it functions in concert with other aryl hydrocarbon and antioxidant response elements. Site-directed promoter mutants are being analyzed to determine the dependence and interdependence of these multiple regulatory elements.
Species 1: Lepidoptera Papilionidae Papilio polyxenes (black swallowtail)
Keywords: aryl hydrocarbons, antioxidants
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