Carcinogen-Metabolizing Enzymes and Insecticides

Abstract

The present study was under taken to demonstrate the effect of some commonly used insecticides on the activity of cytochrome P450 system including cytochrome b5, aryl hydrocarbon [benzo(a)pyrene] hydroxylase (AHH), N-nirosodimethylamine N-demethylase I [NDMA-dI] and NADPH-cytochrome c reductase as phase I of drug oxidation. In addition, the activity of glutathione S-transferase (GST), glutathione reductase (GR), and the level of glutathione (GSH) were determined in the liver of male mice after oral administration of sumithion, dursban, chlordane, methoxychlor, heptachlor epoxide, and lindane as single (24h) or as repeated doses for six consecutive days. Oral administration of sumithion, dursban, chlordane, methoxychlore, and heptachlor epoxide as repeated doses decreased: (i) the hepatic content of cytochrome P450 by 36, 37, 47, 37, and 67%, respectively, (ii) AHH activity by 28, 29, 70, 31, and 79%, respectively, (iii) NDMA-dI activity by 43, 44, 32, 27, and 31, respectively. On the other hand, sumithion, chlordane, and methoxychlore induced the activity of NADPH-cytochrome c reductase by 45, 62, and 43 respectively after repeated dose treatments. In addition, single and repeated-dose treatments of mice with lindane induced: (i) cytochrome P450 by 23 and 65%, respectively, (ii) cytochrome b5 by 49 and 131%, respectively, (iii) AHH activity by 64 and 50%, respectively. Repeated-dose treatments of mice with chlordane, methoxychlore, and heptachlor epoxide decreased the GSH level by 42, 38, and 68%, respectively and GST activity by 44, 44, and 55% respectively. Moreover, single- and repeated-dose treatments of mice with lindane decreased the GSH levels by 40 and 54%, respectively, and induced GST activity by 25 and 41%, respectively. Interestingly, single-dose treatments with chlordane, methoxychlore, and heptachlor epoxide decreased the activity of GR by 32, 38, and 31, respectively whereas repeated doses of these compounds induced such activity by 83, 50, and 64%, respectively. It is concluded that modifications in cytochrome P450 system by pesticides could potentiate the toxicity and carcinogenicity of environmental carcinogens such as polycyclic aromatic hydrocarbon and N-nirosodimethylamine (NDMA).