Differential induction of cytochrome P450 transcripts in Papilio polyxenes by linear and angular furanocoumarins

Abstract

Cytochrome P450 monooxygenases play critical roles in the detoxification of linear and angular furanocoumarins present in the host plants of Papilio polyxenes (black swallowtail) larvae. To determine the spectrum of linear and angular furanocoumarins that induce isozymes responsible for these detoxifications, the metabolic activities of individual P. polyxenes larvae were monitored in response to individual furanocoumarins. Two linear furanocoumarins, xanthotoxin and bergapten, as well as the angular furanocoumarin, angelicin, significantly and selectively induce metabolism of several furanocoumarins. Another angular furanocoumarin, sphondin, does not induce furanocoumarin metabolism even though it is itself capable of being metabolized in vivo. Northern analysis of the mRNAs induced in response to each of four naturally occurring furanocoumarins indicates that mRNAs related to CYP6B1 are highly induced by the two linear furanocoumarins (xanthotoxin, bergapten) and by angelicin, the angular furanocoumarin. RNase protection analysis indicates that CYP6Blv1–3 transcripts, which we have already cloned, are specifically induced by xanthotoxin and that additional CYP6Bl-related transcripts are induced in response to angelicin. These data indicate that a complex array of CYP6B1 transcripts, derived from a minimum of two loci, is responsible for furanocoumarin metabolism in P. polyxenes. Transcripts derived from these loci appear to be differentially induced by linear and angular furanocoumarins.