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Recently, interindividual variations in serum paraoxonase (PON1) activity and the differences in its metabolic activity towards different organophosphates (OPs) caused by the coding region polymorphisms L55M and Q192R have been found to be important risk factors in susceptibility to OP poisoning. In this study, we investigated the effect of PON1 on the outcome of acute OP intoxication and the effect of acute OP intoxication on PON1. Twenty-eight OP-poisoned patients and 66 healthy volunteers were studied. Patients were evaluated for the clinical manifestations of OP intoxication as well as PON1 activity, PON1 mass and PON1 polymorphisms. Butyrylcholine-esterase (BChE) activity was 50% lower (2276±738 U/L versus 5037±1553 U/L, P<0.01) while PON1 activity was 30% lower (114.2±67.4 nmol/mL/min versus 152.9±78.9 nmol/mL/ min, P<0.05) in patients than in controls. We observed that the PON1 and BChE activities of eight of the original subjects returned to normal levels when they were reinvestigated six months after exposure. The frequency of the PON192Q allele was significantly higher in patients than controls (85.7% versus 59.7%, χ2=6.745, P=0.034). QQ/MM individuals had the lowest activity towards paraoxon, while RR/LL individuals had the highest activity. Our data indicate that interindividual differences in PON1 activity and the PON1-55 and-192 polymorphisms are important risk factors in susceptibility to acute OP poisoning; therefore, identifying an individual's PON1 alloenzymes may play an important role in the treatment of patients suffering from OP intoxication.

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The first aim of this study was to evaluate the degree of organophosphorus (OP) pesticides' exposure in viniculture and tobacco production workers via physical examination (neurology and general health aspect) and analysis of paraoxonase (PON1) and butyrylcholinesterase (BuChE) activities. The second aim was to investigate if PON1 polymorphism plays any role in long-term OP exposure. A total of 93 farmers who work as applicators in agriculture were studied. The data were evaluated according to agricultural type, and although the total exposure time was similar in both areas, BuChE and PON1 activities of farmers who work in tobacco production were lower. Overall, BuChE and PON1 activities showed a depletion in the farmer group compared to age-matched controls. When the farmers were categorized according to the number of their symptoms, the BuChE activities of farmers who had two or more symptoms were found to be depleted (n = 43, 2948 +/- 756) compared to farmers who had one or no symptoms (n = 37, 3356 +/- 659). Allele frequencies of patients and controls for positions 55 and 192 were similar to Turkish population data and there was no association between the allele polymorphism and symptoms/signs of long-term exposure. Our results indicate that there is an important inhibition of PON1 activity in chronic OP poisoning, and this together with BuChE activity might well be used as a reliable index of chronic exposure to OP.

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