Implications of paraoxonase-1 (PON1) activity and polymorphisms on biochemical and clinical outcomes in workers exposed to pesticides

Paraoxonase-1 (PON1) is known to play an important role in the individual susceptibility to environmental chemicals, particularly pesticides. The major results of our studies on biochemical and clinical end-points of workers long-term exposed to pesticides in a large intensive agriculture area from Southeast Spain are presented herein and compared with several other epidemiologic studies performed in different scenarios. In addition of being an individual marker of susceptibility, PON1 can be also considered a biological indicator of exposure to pesticides, since workers spraying these agents (chiefly OPs) showed decreased enzyme levels. Besides, long-term exposure to pesticides appears to indirectly elicit higher levels of PON1, which might be regarded as enzyme induction. On the other hand, carriers of the PON1 192R allele showed lower levels of erythrocyte cholinesterase and catalase, but a higher glutathione reductase activity. Regarding clinical outcomes, workers with the PON1 R allele had less risk of reporting a previous episode of pesticide poisoning as well as a lower risk of pesticide-related symptomatology. Exposure to low doses of pesticides which are metabolically activated in the liver seems to elicit subtle and early biochemical changes of hepatotoxicity. It is concluded that epidemiological studies addressing health or biochemical outcomes of workers occupationally exposed to pesticides should determine PON1 genotypes and phenotypes (activities), as these biomarkers may help in identifying those individuals at increased risk of developing pesticide toxicity or who are showing early effects after pesticide exposure.