Dinitropyrene nitroreductase activity of purified NAD(P)H-quinone oxidoreductase: role in rat liver cytosol and induction by Aroclor-1254 pretreatment.
Dinitropyrenes (DNP) are potent bacterial mutagens in the Ames test and genotoxins in cultured mammalian cells. Rat liver cytosol contains nitroreductases that are critical in the activation of DNP to the ultimate DNA-binding species. In order to study the nature and inducibility of liver cytosolic enzymes involved in the activation of DNP, cytosolic nitroreductase activities towards three DNP isomers (1,3-, 1.6- and 1,8-DNP) were determined in Aroclor-pretreated and untreated rats. Aroclor-1254 pretreatment resulted in up to 5-fold induction of cytosolic DNP nitroreductase. This induction was reflected in at least a 15-fold increase in cytosolic NAD(P)H-quinone oxidoreductase (NQOR) (E.C. 1.6.99.2) activity. The rates of nitroreduction for the three DNP isomers followed the order 1,6- greater than 1,8- greater than 1,3-DNP in all cases studied. 1,6-DNP nitroreductase coeluted with NQOR activity upon affinity purification. Highly purified NQOR catalyzed the NADH- and NADPH-dependent reduction of each of the three DNP isomers and displayed the same stereospecificity as the cytosolic activity. These results provide evidence that NQOR participates in the cytosolic nitroreduction of DNP and constitutes a major part of the total DNP nitroreductase activity upon induction of NQOR by Aroclor-1254 pretreatment. Thus, the role of NQOR in the metabolism of these mutagens depends significantly upon the degree to which this enzyme is induced.
Hajos
A K
AK
Department of Biochemistry, Louisiana State University, Baton Rouge 70803.
Winston
G W
GW
D000818:Animals; D001140:Aroclors / Q000494:pharmacology*; D020111:Chlorodiphenyl (54% Chlorine); D003600:Cytosol / Q000201:enzymology; D004790:Enzyme Induction; D008099:Liver / Q000201:enzymology; D008297:Male; D016660:NAD(P)H Dehydrogenase (Quinone); D009249:NADP / Q000378:metabolism; D009601:Nitroreductases / Q000096:biosynthesis / Q000378:metabolism*; D011721:Pyrenes / Q000378:metabolism; D011808:Quinone Reductases / Q000096:biosynthesis / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D001140:Aroclors; D011721:Pyrenes; D020111:Chlorodiphenyl (54% Chlorine); D009249:NADP; D016660:NAD(P)H Dehydrogenase (Quinone); D011808:Quinone Reductases; C068284:dinitropyrene nitroreductase; D009601:Nitroreductases