Characterization of CYP1A in hepatocytes of cynomolgus monkeys (Macaca fascicularis) and induction by different substituted polychlorinated biphenyls (PCBs).
Cynomolgus monkeys (Macaca fascicularis) have been used previously as a model to study effects on cytochrome P450 (CYP) regulation. Until now it has not been elucidated which CYP1A proteins are present in this primate species. The aim of this study was to characterize CYP1A in untreated hepatocytes of cynomolgus monkey using two specific CYP1A inhibitors (alpha-naphthoflavone and furafylline). The effect of different substituted polychlorinated biphenyls (PCBs) on CYP1A regulation was also studied in these hepatocytes. Small quantities of CYP1A2 have been identified in untreated hepatocytes. Northern blots showed the presence of a CYP1A mRNA in untreated hepatocytes, when hybridizations where performed with human CYP1A2 cDNA. Inhibitions with furafylline and alpha-naphthoflavone also suggested the presence of CYP1A2 properties. After induction with different PCBs, (probably) CYP1A1 mRNA and enzyme activity were induced in cynomolgus monkey hepatocytes. As expected, 2,3',4,4',5-PeCB (PCB no. 118), a mono-ortho substituted congener, was a potent CYP1A inducer but 2,2',3,4,4',5',5'-HpCB (PCB no. 180), a di-ortho and 2,2',3,4',5,5',6-HpCB (PCB no. 187), a tri-ortho substituted PCB, could induce CYP1A mRNA and enzyme activity in cynomolgus monkey hepatocytes as well.
Van Der Burght
A S
AS
Research Institute of Toxicology, Utrecht University, The Netherlands.
Kreikamp
A P
AP
Horbach
G J
GJ
Seinen
W
W
Van Den Berg
M
M
D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D019363:Cytochrome P-450 CYP1A1 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D019388:Cytochrome P-450 CYP1A2 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D004790:Enzyme Induction / Q000187:drug effects*; D008099:Liver / Q000201:enzymology*; D008252:Macaca fascicularis; D011078:Polychlorinated Biphenyls / Q000494:pharmacology*; D011506:Proteins / Q000032:analysis; D012313:RNA / Q000032:analysis / Q000302:isolation & purification; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats
D011506:Proteins; D012333:RNA, Messenger; D012313:RNA; D011078:Polychlorinated Biphenyls; D019363:Cytochrome P-450 CYP1A1; D019388:Cytochrome P-450 CYP1A2