An unusual profile of musk xylene-induced drug-metabolizing enzymes in rat liver.
We have demonstrated previously that musk xylene, a non-mutagenic carcinogen, is a novel and specific inducer of CYP1A2 in rats (Iwata et al., Biochem Biophys Res Commun 184: 149-153, 1992). In the present study, the effects of musk xylene (50, 100 or 200 mg/kg body weight, i.p., for 5 consecutive days) on both Phase I and Phase II metabolizing enzymes in rat liver were investigated further and more completely. Among the mixed-function oxidases monitored, 7-ethoxycoumarin deethylase and 7-pentoxyresorufin depentylase activities were increased at all dose levels from 1.6- to 1.7-fold and 2.6- to 3.1-fold, respectively. Benzo[a]pyrene hydroxylase activity was increased significantly at only the 200 mg/kg dose level of musk xylene (1.5-fold). Regarding Phase II enzymes, activities of both cytosolic DT-diaphorase and glutathione S-transferase (GST) were increased up to 2.0- to 2.4-fold by musk xylene in a dose-dependent manner. Western blot analysis revealed that the changes in these activities were caused by increases in the amounts of DT-diaphorase and GST Ya subunit. Microsomal UDP-glucoronyltransferase (UDPGT) activity assayed with p-nitrophenol as substrate was increased 1.6- to 2.0-fold. These results show that musk xylene induces both Phase I cytochrome P450 mixed-function oxidase (CYP1A2 specific) and Phase II metabolizing enzyme systems (DT-diaphorase, GST Ya subunit and UDPGT) in rat liver.
Iwata
N
N
Division of Xenobiotic Metabolism and Disposition, National Institute of Hygiene Sciences, Tokyo, Japan.
Minegishi
K
K
Suzuki
K
K
Ohno
Y
Y
Igarashi
T
T
Satoh
T
T
Takahashi
A
A
D000818:Animals; D001835:Body Weight; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D015786:Cytochromes b5 / Q000096:biosynthesis; D008058:Dihydrolipoamide Dehydrogenase / Q000096:biosynthesis; D004790:Enzyme Induction / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D014992:Xylenes / Q000494:pharmacology*
D014992:Xylenes; C031447:musk xylene; D015786:Cytochromes b5; D003577:Cytochrome P-450 Enzyme System; D008058:Dihydrolipoamide Dehydrogenase