Resorufin inhibits the in vitro metabolism and mutagenesis of benzo(a)pyrene.
7-Hydroxyphenoxazin-3-one, commonly known as resorufin, strongly inhibits benzo(a)pyrene-induced mutation in the Ames bacterial reversion assay. The antimutagenic mechanism is due in part to redox cycling of resorufin with the concommitant transfer of reducing equivalents from NADPH to molecular oxygen. The diversion of electrons from cytochrome P-450 enzymes results in a large decrease in the percent of benzo(a)pyrene metabolized by rat liver microsomes as measured by HPLC. Resorufin stimulated a non-stoichiometric consumption of NADPH and was reduced in S-9 or microsomal solutions. These processes were sensitive to dicumarol and NADP inhibition to different degrees in each liver fraction. This suggests two pathways are involved in resorufin redox cycling, one involving DT-diaphorase and the other with NADPH cytochrome P-450 reductase. Oxygen was shown to be an electron acceptor for S-9 mediated resorufin redox cycling, but was not consumed by a microsomal solution in the presence of resorufin and NADPH.
Jablonski
J E
JE
Sullivan
P D
PD
D000818:Animals; D001564:Benzo(a)pyrene / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D001728:Dicumarol / Q000494:pharmacology; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D009152:Mutagenicity Tests; D009243:NAD / Q000378:metabolism; D016660:NAD(P)H Dehydrogenase (Quinone); D009249:NADP / Q000378:metabolism / Q000494:pharmacology; D009251:NADPH-Ferrihemoprotein Reductase / Q000037:antagonists & inhibitors / Q000378:metabolism; D010078:Oxazines / Q000494:pharmacology*; D010084:Oxidation-Reduction; D011808:Quinone Reductases / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D010078:Oxazines; D009243:NAD; D001564:Benzo(a)pyrene; D009249:NADP; C014180:resorufin; D001728:Dicumarol; D003577:Cytochrome P-450 Enzyme System; D009251:NADPH-Ferrihemoprotein Reductase; D016660:NAD(P)H Dehydrogenase (Quinone); D011808:Quinone Reductases