Effect of arsenite on the induction of CYP1A4 and CYP1A5 in cultured chick embryo hepatocytes.
We had reported previously that 2.5-5 microM sodium arsenite decreased the phenobarbital-mediated induction of CYP2H activity and protein but not CYP2H1 mRNA in chick-embryo hepatocyte cultures. Induction of a CYP1A activity and protein by 3-methylcholanthrene was also decreased by low arsenite concentrations; however, CYP1A mRNAs were not measured in those studies. We report here that low concentrations of arsenite decreased induction of activities and mRNAs of two chicken cytochromes P450, CYP1A (1A4 and 1A5), by 3-methylcholanthrene in chick-embryo hepatocyte cultures. Arsenite treatment did not affect the turnover of either mRNA, nor did it decrease the superinduction of each mRNA caused by treatment with cycloheximide in addition to 3-methylcholanthrene. Glutathione depletion enhanced the effect of arsenite to decrease induction of CYP1A4. These results indicate the induction of CYP1A4 and 1A5 is inhibited by sodium arsenite at the level of transcription, suggesting that the Ah receptor complex may be involved.
Jacobs
J M
JM
Veterans Administration Medical Center, White River Junction, VT 05009-0001, USA.
Nichols
C
C
Marek
D
D
Gorman
N
N
Walton
H S
HS
Sinclair
P R
PR
Sinclair
J F
JF
D000818:Animals; D018053:Arsenites / Q000633:toxicity*; D001189:Aryl Hydrocarbon Hydroxylases; D030161:Avian Proteins; D002478:Cells, Cultured; D002642:Chick Embryo; D003513:Cycloheximide / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis* / Q000378:metabolism; D004790:Enzyme Induction / Q000187:drug effects; D005978:Glutathione / Q000502:physiology; D022781:Hepatocytes / Q000187:drug effects / Q000201:enzymology*; D007202:Indicators and Reagents; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000096:biosynthesis* / Q000378:metabolism; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D014577:Uroporphyrinogens / Q000096:biosynthesis
D018053:Arsenites; D030161:Avian Proteins; D007202:Indicators and Reagents; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D014577:Uroporphyrinogens; D003577:Cytochrome P-450 Enzyme System; D003513:Cycloheximide; D010088:Oxidoreductases; D001189:Aryl Hydrocarbon Hydroxylases; C416342:CYP1A4 protein, Gallus gallus; C108015:cytochrome P-450 CYP1A5; D005978:Glutathione; C015001:arsenite