Effects of acetone administration on cytochrome P-450-dependent monooxygenases in hamster liver, kidney, and lung.
The effects of acetone on liver, kidney, and lung monooxygenases were studied using hamsters administered 8% acetone in drinking water. Binding of aniline to liver microsomes induced a type II difference spectrum, and the spectral binding was enhanced in hamsters pretreated with acetone. Administration of acetone caused significant increases of cytochrome P-450 and cytochrome b5 contents in liver microsomes. The increases of the hemeproteins were associated with induction of monooxygenase activities toward test substrates, aniline, N-nitrosodimethylamine, benzphetamine, benzo(a)pyrene, and 7-ethoxycoumarin. In the kidneys, acetone administration increased microsomal contents of the hemeprotein and monooxygenase activities toward aniline. N-nitrosodimethylamine, and 7-ethoxycoumarin, but not benzphetamine or benzo(a)pyrene. In the lungs, acetone pretreatment increased aniline hydroxylase activity without affecting the levels of N-nitrosodimethylamine demethylase, cytochromes P-450 and b5. In marked contrast to the inductive effects in the liver, acetone administration markedly decreased lung microsomal benzo(a)pyrene hydroxylase and 7-ethoxycoumarin O-deethylase activities. Gel electrophoresis of liver and kidney microsomes from control and acetone-treated hamsters revealed that acetone treatment enhanced the intensity of a protein band(s) in the cytochrome P-450 molecular weight region. Immunoblotting of the microsomal proteins showed that the protein band induced by acetone in hamster liver, kidney and lung was cross-reactive with antibody raised against ethanol-inducible human liver cytochrome P-450. These results demonstrate that acetone has the ability to uniformly induce a specific form of cytochrome P-450, designated as IIE1, and to cause differential changes of monooxygenase activities in the hamster tissues.(ABSTRACT TRUNCATED AT 250 WORDS)
Ueng
T H
TH
Department of Biochemistry, College of Medicine, National Taiwan University, Taipei, ROC.
Tsai
J N
JN
Ju
J M
JM
Ueng
Y F
YF
Iwasaki
M
M
Guengerich
F P
FP
D000096:Acetone / Q000494:pharmacology*; D000818:Animals; D006224:Cricetinae; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects*; D004591:Electrophoresis, Polyacrylamide Gel; D004790:Enzyme Induction; D015151:Immunoblotting; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008168:Lung / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D008647:Mesocricetus; D010105:Oxygenases / Q000187:drug effects*
D000096:Acetone; D003577:Cytochrome P-450 Enzyme System; D010105:Oxygenases