INDUCTION OF CYTOCHROME-P-450 ACTIVITIES BY NICOTINE IN THE TOBACCO HORNWORM, MANDUCA-SEXTA

The induction by dietary nicotine of a series of cytochrome P-450 enzyme activities was investigated in early fifth-instar Manduca sexta larvae. At a low nicotine concentration in the diet (0.1%), three of 12 midgut microsomal enzyme activities were significantly increased. At a higher concentration (0.75%) commonly found in plants of the genus Nicotiana, nine of 12 activities were induced by 1.4- to 10.0-fold. Total cytochrome P-450, P-450 reductase activity, and midgut microsomal metabolism of nicotine were also increased by feeding 0.75% nicotine. Nicotine was metabolized by midgut microsomes to nicotine-1-N-oxide and cotinine-N-oxide. Fat body microsomal nicotine metabolism was low and unaffected by dietary nicotine. Isolated nerve cords were able to metabolize nicotine in vitro but this metabolism was not inducible by dietary nicotine. Nicotine-fed fifth-instar M. sexta larvae showed an increased tolerance to subsequent nicotine injection when compared to larvae fed a control diet. These results support the idea that induction of midgut cytochrome P-450-related metabolism is an adaptation of Manduca sexta to dietary nicotine.