INDUCTION BY ALKALOIDS AND PHENOBARBITAL OF FAMILY-4 CYTOCHROME P450 IN DROSOPHILA - EVIDENCE FOR INVOLVEMENT IN HOST-PLANT UTILIZATION

In vertebrates, cytochrome P450s of the CYP2 and CYP3 families play a dominant role in drug metabolism, while in insects members of the CYP6 and CYP28 families have been implicated in metabolism of insecticides and toxic natural plant compounds. A degenerate 3' RACE strategy resu lted in the identification of fifteen novel P450s from an alkaloid-res istant species of Drosophila. The strong (17.4-fold) and highly specif ic induction of a single gene (CYP4D10) by the toxic isoquinoline alka loids of a commonly utilized host-plant (saguaro cactus) provides the first indication that members of the CYP4 family in insects may play a n important role in the maintenance of specific insect-host plant rela tionships. Strong barbiturate inducibility of CYP4D10 and two other D. mettleri P450 sequences of the CYP4 family was also observed, suggest ing a pattern of xenobiotic responsiveness more similar to those of se veral vertebrate drug-metabolizing enzymes than to putative vertebrate CYP4 homologs.