BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS Pages 59-65 ROLE OF ISOSAFROLE AS COMPLEXING AGENT AND INDUCER of P-450LQ IN RABBIT LIVER MICROSOMES

SUMMARY: Isosafrole serves as an excellent inducing agent in rabbits for Wq, the same isozyme as that which is induced by 3-methylcholanthrene and 5,6-benzoflavone. Since the isosafrole adduct formed with isozyme 4 is unstable, the uncomplexed cytochrome may be purified in very good yield (over 30%, based on total P-450) from liver microsomes of animals given this agent. Isosafrole forms adducts with both isozyme 2 (the phenobarbital-inducible form of P-450) and isozyme 4 in the reconstituted system containing NADPH-cytochrome P-450 reductase, phosphatidylcholine, and NADPH under aerobic conditions, but with the latter cytochrome the reaction has a lower Km and maximal rate. The addition of synergists to insecticides has a sparing action, so that lower doses of the insecticide then have the same effect (11. Many synergists were found to exhibit substrate binding spectra upon addition to hepatic microsomes (21, and it was proposed that the methylenedioxyphenyl synergists may act by affecting the integrity of the electron transfer chain