DIFFERENTIAL RESPONSES OF HEPATIC MONOOXYGENASES AND GLUTATHIONE S-TRANSFERASES OF MICE TO A COMBINATION OF CADMIUM AND NICKEL

The acute combined effects of cadmium (Cd) and nickel (Ni) on hepatic monooxygenase activities (ethylmorphine N-demethylase, EMND; aminopyri ne N-demethylase, AMND; aniline 4-hydroxylase, AH), cytochrome P-450, cytochrome b(5), microsomal heme and reduced glutathione (GSH) levels and glutathione S-transferase (GST) activities toward several substrat es (1-chloro-2,4-dinitrobenzene, CDNB; 1,2-dichloro-4-nitrobenzene, DC NB; ethacrynic acid, EAA; 1,2-epoxy-3-(p-nitrophenoxy)-propane, ENPP) were determined and compared with those of Cd or Ni alone in mice. Mal e adult mice (25-30 g) were administered either a single dose of Cd (3 .58 mg CdCl2 . H2O/kg, i.p.) 48 hr prior to killing or a single dose o f Ni (59.5 mg NiCl2 . H2O/kg, s.c.) 16 hr prior to killing. For the co mbined treatment, the animals received the single dose of Ni 32 hr aft er the single dose of Cd and were then killed 16 hr later. Cd treatmen t alone significantly decreased EMND, AMND, and AH activities and cyto chrome P-450 and heme levels as compared with controls. Cytochrome b(5 ) level was not altered by Cd treatment. Cd also inhibited GSH level a nd the GST activities toward CDNB, EAA and ENPP significantly. No sign ificant change was observed in the GST activity for DCNB by Cd. Ni tre atment alone, however, decreased the monooxygenase and GST activities studied, and cytochrome P-450, cytochrome b(5), heme and GSH levels si gnificantly. Combined treatment significantly depressed the monooxygen ase activities and cytochromes and heme levels. GSH level was not sign ificantly altered. Combined treatment, however, significantly increase d GST activities toward CDNB and DCNB, did not alter the GST activity for EAA and significantly inhibited the GST activity toward ENPP, but not to a greater degree than noted by Ni treatment alone.