Cytochrome P450 1A1 (CYP1A1) in blood lymphocytes evidence for catalytic activity and mRNA expression.
Studies initiated to characterise the catalytic activity and expression of CYP1A1 in rat blood lymphocytes revealed significant activity of 7-ethoxyresorufin-O-deethylase (EROD) in rat blood lymphocytes. Pretreatment with 3-methylcholanthrene (MC) and beta-naphthoflavone (NF) resulted in significant induction in the activity of lymphocyte EROD suggesting that like the liver enzyme, EROD activity in lymphocytes is inducible and is mediated by the MC inducible isoenzymes of P450. The increase in the activity of EROD was associated with a significant increase in the apparent Vmax and affinity of the substrate towards EROD. That this increase in the activity of EROD could be primarily due to the increase in the expression of CYP1A1 isoenzymes was demonstrated by RT-PCR and western immunoblotting studies indicating an increase in the expression of CYP1A1 in blood lymphocytes after MC pretreatment. Significant inhibition in the EROD activity of MC induced lymphocyte by anti-CYP1A1/1A2 and alpha-naphthoflavone further provided evidence that the CYP1A1/1A2 isoenzymes are involved in the activity of EROD in blood lymphocytes. The data indicating similarities in the regulation of CYP1A1 in blood lymphocytes with the liver isoenzyme suggests that factors which may affect expression of CYP1A1 in liver may also affect expression in blood lymphocytes and that blood lymphocytes could be used as a surrogates for studying hepatic expression of the xenobiotic metabolising enzymes.
Dey
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Industrial Toxicology Research Centre, Mahatma Gandhi Marg, Lucknow, UP, India.
Parmar
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Dayal
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Dhawan
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Seth
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D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001571:Benzoflavones / Q000494:pharmacology; D015153:Blotting, Western; D002273:Carcinogens / Q000494:pharmacology; D002384:Catalysis; D019363:Cytochrome P-450 CYP1A1 / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*; D004790:Enzyme Induction / Q000187:drug effects; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D008214:Lymphocytes / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D008748:Methylcholanthrene / Q000494:pharmacology; D008862:Microsomes, Liver / Q000201:enzymology; D010078:Oxazines / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019324:beta-Naphthoflavone / Q000494:pharmacology
D000906:Antibodies; D001571:Benzoflavones; D002273:Carcinogens; D007527:Isoenzymes; D010078:Oxazines; D012333:RNA, Messenger; D008748:Methylcholanthrene; C007649:ethoxyresorufin; C011512:alpha-naphthoflavone; D019324:beta-Naphthoflavone; D019363:Cytochrome P-450 CYP1A1