Enzyme induction, pesticides

Agarwal et al. 1978), the quantification of these specific enzymes may indicate that exposure to endosulfan has occurred. Blood tests, such as decay curves for aminopyrine in plasma, which are semiquantitative indices of liver enzyme induction, have been used successfully in the past to demonstrate enzyme induction in pesticide-exposed workers. Because numerous chemicals found at hazardous waste sites also induce these hepatic enzymes, these measurements are not specific for endosulfan exposure. However, measurements of enzyme activity, together with the detection of the parent compound or its metabolites in tissue or excreta, can be useful indicators of exposure. All of these potential biomarkers require further verification in epidemiological studies. Further studies with focus on the development of methods to separate and measure the estrogenicity of endosulfan in in vitro assays would be valuable since these assays are more sensitive and discriminative than other conventional biomarkers. Preliminary results have been presented by Sonnenschein et al. (1995). 

Urinary D-glucaric acid levels have been shown to be a sensitive indicator of microsomal enzyme induction in workers exposed to chlordecone (Guzelian 1985). However, other substances such as barbiturates, phenytoin, chlorbutanol, aminopyrine, phenylbutazone, and contraceptive steroids as well as other organochlorinated pesticides also cause microsomal enzyme induction and cause changes in urinary D-glucaric acid (Morgan and Roan 1974). 

Chadwick RW, Chadwick CJ, Freal JJ, et al. 1977. Comparative enzymes induction and lindane metabolism in rats pre-treated with various organochlorine pesticides. Xenobiotica 7(4) 235-246. 

Metals have been shown to dramatically alter CYP concentrations, but there have not been any studies examining the effects on pesticide biotransformation. In contrast, several studies have examined the effects of enzyme induction on pesticide biotransformation. Pre-exposure of channel catfish to the PCB mixture Aroclor 1254 failed to alter the biotransformation of chlorpyrifos or parathion81. As mentioned above, the fungicide propioconizole induced the activation of parathion to the oxon in fathead minnow53. 

Adaptation of microorganisms to pesticides in surface soils is a process that includes examples of population growth and enzyme induction as contributing factors. Introduced microbial agents have some potential for detoxification of pesticides in groundwater, but the low level of nutrients in aquifers contaminated with trace levels of pesticides limits microbial activity and may reduce the effectiveness of introduced microorganisms. 

Enzyme induction is an increase in enzyme activity as a result of increased concentration of enzyme protein. Hundreds of chemicals have been shown to induce CYP450 and other enzymes. Most of these are Upophiles. These include pharmaceuticals, hormones, organochlorine pesticides, PAHs, including PCBs, and other carcinogenic species [3]. Some pesticides and their decomposition products are powerful inducers. Mirex induces at levels as low as 1 mg/kg. TCDD induces at a level of 1 ig/kg in some animal species. 

Den Tonkelaar EM, Van Esch GJ. 1974. No-effect levels of organochlorine pesticides based on induction of microsomal liver enzymes in short-term toxicity experiments. Toxicology 2 371-380. 

Hodgson E, Kulkarni AP, Fabacher DL, et al. 1980. Induction of hepatic drug metabolizing enzymes in mammals by pesticides A review. J Environ Sci Health B 15(6) 723-754. 

Hodgson, E., and Philpot, R. M. Interaction of methylenedioxyphenyl (1,3-benzodioxole) compounds with enzymes and their effects on mammals. Drug Metab. Rev. 3, 231,1974. Hodgson, E. Induction and inhibition of pesticide-metabolizing enzymes Roles in synergism of pesticides and pesticide action. Toxicol. Ind. Health 15, 6,1999. 

Blizard, D., T. Sueyoshi, M. Negishi, S.S. Dehal and D. Kupfer. Mechanism of induction of cytochrome P450 enzymes by the proestrogenic endocrine disruptin pesticide-methoxychlor interactions of methoxychlor metabolites with the constitutive androstane receptor system. Drug Metab. Dispos. 29 781-785, 2001. 

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