Induction of cytochrome P450 1A1 and 1A2 by hyperoxia.
The effect of hyperoxia (O2 > 95%) for 48 hours on the induction of pulmonary and hepatic cytochrome P450 has been investigated in adult male rats. Northern blot analysis using six "specific" oligonucleotide probes indicated that CYP 1A1 and CYP 1A2 mRNAs in liver and CYP 1A1 mRNA in lung were significantly increased by hyperoxic exposure, whereas the major constitutive P450 mRNAs, CYP 2C11 in liver and CYP 2B1 in lung, were decreased. Since induction of CYP 1A1 has only been reported with the use of exogenously administered xenobiotics, further studies were carried out to confirm the results obtained with Northern blot analysis. cDNAs were synthesized for CYP 1A1 and 1A2 in the liver and CYP 1A1 in the lungs and amplified by reverse PCR. These results indicate that these cDNAs were amplified significantly more in the hyperoxia group than in the control animals. Futhermore, CYP 1A1 and 1A2 proteins in liver and CYP 1A1 protein in lungs as well as the corresponding monooxygenase activities were increased by hyperoxia. Hyperoxic induction of CYP 1A1 and 1A2 is the first demonstration of nonexogenous CYP 1A induction in animals and indicates the needs to pursue the changes of Ah receptor-ligand-DNA interaction in hyperoxia.
Okamoto
T
T
Department of Pathology, College of Medicine, University of California, Irvine 92717.
Mitsuhashi
M
M
Fujita
I
I
Sindhu
R K
RK
Kikkawa
Y
Y
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases; D001483:Base Sequence; D015152:Blotting, Northern; D015153:Blotting, Western; D001835:Body Weight; D019363:Cytochrome P-450 CYP1A1; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis* / Q000378:metabolism; D003579:Cytochrome Reductases / Q000378:metabolism; D042966:Cytochrome-B(5) Reductase; D004435:Eating; D004790:Enzyme Induction; D015870:Gene Expression / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008168:Lung / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D008969:Molecular Sequence Data; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism; D015345:Oligonucleotide Probes; D010088:Oxidoreductases / Q000378:metabolism; D010100:Oxygen / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D013250:Steroid Hydroxylases / Q000096:biosynthesis*
D015345:Oligonucleotide Probes; D012333:RNA, Messenger; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; D013250:Steroid Hydroxylases; D001189:Aryl Hydrocarbon Hydroxylases; D019363:Cytochrome P-450 CYP1A1; C029009:steroid hormone 7-alpha-hydroxylase; D003579:Cytochrome Reductases; D042966:Cytochrome-B(5) Reductase; D009251:NADPH-Ferrihemoprotein Reductase; D010100:Oxygen