Carboxylic esterase and its associations with long-term effects of organophosphorus pesticides.
OBJECTIVE
To examine a) the effect of organophosphorus pesticide exposure on activity of carboxylic esterases, namely butyrylcholinesterase (BChE), carboxylesterase (CarbE) and paraoxonase (PonE); and b) the association of polymorphisms of BChE and PonE with individual genetic susceptibility to organophosphorus pesticide exposure.


METHODS
A cross-sectional study was conducted in 75 workers exposed to organophosphorus pesticides and 100 non-exposed controls. The serum activity of these enzymes was measured. Variant forms of BCHE-K, PON-192, and PON-55 were detected. A symptom score was developed as a proxy measure of clinical outcomes.


RESULTS
Activities of both BChE and CarbE were lower in exposed workers (27.3+/-21.65 nmolxh(-1)xmL(-1) and 235.6+/-104.03 nmolxmin(-1)xmL(-1)) than in non-exposed workers (78.313+/-30.354 nmolxh(-1)xmL(-1) and 362.681+/-194.997 nmolxmin(-1)xmL(-1)). The activity of PonE was not associated with exposure status. The AChE activity in the exposed workers with BCHE-K genotype UU (61 cases), genotype UK (12 cases) and genotype KK (2 cases) was 105.05, 84.42 and 79.00 mmolxh(-1)xmL(-1), respectively and the accumulative symptom scores were 3.74, 9.17, and 12.50 accordingly. The AChE activity in the exposed workers with PON-192 genotypeBB (37), genotype AB (27) and genotype AA (11) was 116.8, 91.2, and 72.3 mmolxh(-1)xmL(-1), respectively and the symptom scores were 2.00, 6.74, and 9.73 accordingly. The AChE activity in those with PON-55 genotype LL (70) and genotype LM (5) was 102.4 and 82.8 mmolxh(-1)xmL(-1) and the symptom scores were 4.53 and 9.20. The symptom score was the highest in individuals with abnormal homozygote for each of the three gene loci.


CONCLUSIONS
Long-term exposure to organophosphorus pesticides can inhibit BChE and CarbE activity, but exerts no inhibitory effect on PonE activity. Different genotypes of BCHE-K, PON-192, and PON-55 may be related to the severity of adverse health effects of organophosphorus pesticide exposure. Implications of potentially higher susceptibility of workers with mutant homozygotes should be evaluated to reduce health risks.
Zhou
Zhi-Jun
ZJ
Dept. of Occupational Health and Toxicology, School of Public Health, WHO Collaborating Center for Occupational Health / Key Laboratory of Public Health and Safety, Ministry of Education, Fudan University, Shanghai 200032, China. zjzhou@shmu.edu.cn
Zheng
Jie
J
Wu
Qiang-En
QE
Xie
Fang
F
D000328:Adult; D001483:Base Sequence; D002091:Butyrylcholinesterase / Q000187:drug effects*; D043182:Carboxylesterase / Q000037:antagonists & inhibitors*; D017931:DNA Primers; D004781:Environmental Exposure; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009943:Organophosphorus Compounds / Q000633:toxicity*; D010575:Pesticides / Q000633:toxicity*; D016133:Polymerase Chain Reaction
D017931:DNA Primers; D009943:Organophosphorus Compounds; D010575:Pesticides; D043182:Carboxylesterase; D002091:Butyrylcholinesterase