Disturbance of microsomal detoxication mechanisms in liver by chlorophenol pesticides.
The pesticide pentachlorophenol known as an uncoupler of mitochondrial oxidative phosphorylation was shown to disturb liver microsomal detoxication functions by a selective inhibition of the terminal oxygenation enzyme P-450. At lower concentrations the flavin moiety of this enzyme chain is not inhibited but rather is stimulated, whereby a qualitative shift in detoxication of aromatic amines from C-oxygenation to N-oxygenation is obtained. The effects were due to the pentachlorophenol itself and not to a metabolite. Similar effects of varying strength were also obtained with other chlorophenol pesticides; 2,4,di-, 2,4,6,-tri and 2,3,4,6-tetrachlorophenol, di- and hexachlorophen, tri- and nonachloro-2-hydroxydiphenyl ethers. The relevance of these findings to the possible synergistic influence of chlorophenols on the carcinogenic effects of polyaromatic amines and hydrocarbons is discussed.
D000814:Aniline Compounds / Q000378:metabolism; D000818:Animals; D001711:Biotransformation; D002733:Chlorophenols / Q000494:pharmacology*; D003864:Depression, Chemical; D008658:Inactivation, Metabolic; D007306:Insecticides / Q000494:pharmacology*; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D008930:Mitochondria, Liver / Q000378:metabolism; D010085:Oxidative Phosphorylation / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D013997:Time Factors
D000814:Aniline Compounds; D002733:Chlorophenols; D007306:Insecticides