Comparison of cytochrome P-450-dependent metabolism in different developmental stages of drosophila melanogaster

Abstract

The activities of several drug metabolizing enzymes were compared in microsomes from larvae and adult Drosophila. The cytochrome P-450 content and the benzo[a]pyrene (BP) hydroxylation, p-nitroanisole demethylation and 3- and 4-hydroxylation of biphenyl were 4–20-fold higher in microsomes from adult flies, while 7-ethoxycoumarin deethylase activity and cytochrome c reductase activity were about the same in the two stages. 2-OH-biphenyl was formed in trace amounts by microsomes from adult flies but not to any detectable amount by microsomes from larvae. Pretreatment with phenobarbital (PB), Aroclor 1254 (PCB) or β-naphthoflavone (BNF) increased the cytochrome P-450 content and the various cytochrome P-450-mediated reactions up to 7-fold in larvae. The effects of the pretreatments were weaker in adult flies, where the increase never was more than 3-fold, and many reactions were unaffected by the pretreatments. BNF was thus inefficient in enhancing all reactions, except a slight (1.3-fold) increase in the formation of 4-OH-biphenyl. Microsomes from both stages exhibited increases in specific protein bands with apparent molecular weights of 51 000–58 000 in the sodium dodecyl sulphate (SDS)-polyacrylamide gel electrophoresis following treatment with PB, PCB and BNF. Differences were observed between larvae and adults with respect both to the number of and the molecular weights of the increased protein bands.