Aging modifies the expression of hepatic microsomal cytochromes P-450 after pretreatment of rats with beta-naphthoflavone or phenobarbital.

The various forms of hepatic cytochrome P-450 respond differentially to aging and induction. We examined the levels of six forms of cytochrome P-450, designated as Forms 1 through 5 and Form b, as a function of age and induction. Radial immunodiffusion analysis of rat liver microsomes indicate that cytochrome P-450 Forms 1 and 2 respond to induction by beta-naphthoflavone or phenobarbital less well in aging rats than in young rats. beta-naphthoflavone is less effective in inducing Forms 3, 4, and 5 in aging rats than in young rats. Phenobarbital, however, is more effective in inducing Forms 3 and 4 in aging rats than in young rats but does not induce Form 5 in either young or aging rats. Although Form b is induced predominantly by phenobarbital, beta-naphthoflavone induces Form b moderately in aging rats. Phenobarbital induces Form b to approximately the same extent in aging rats and in young rats. In untreated rats Form 2 is the predominant form, while Forms 1 and 3 are present in moderate amounts. The results of the immunodiffusion analysis were confirmed by the resolution and partial purification of cytochromes P-450 from microsomes of aging and young rats pretreated with beta-naphthoflavone or phenobarbital. These results identify changes with age in specific forms of cytochrome P-450 as a function of the aging process in rats.