title: Changes in erythrocyte enzymes in humans long-term exposed to pesticides: influence of several markers of individual susceptibility.
abstract: Changes in erythrocyte delta-aminolevulinic acid dehydratase (ALA-D) have been reported after exposure to different pesticides, including organophosphates and paraquat. In this study, we have determined ALA-D in 135 pesticide applicators (sprayers) from an intensive agriculture setting at two periods with different pesticide exposure. Acetylcholinesterase (AChE) was used as a reference biomarker. The effects of the combined polymorphism of enzymes involved in the detoxification of pesticides (paraoxonase (PON1), benzoylcholinesterase (BChE), and glutathione S-transferase (GSTM1 and GSTT1)) on the level of the target erythrocyte enzymes were also studied as biomarkers of individual susceptibility. Sprayers presented significant lower levels of ALA-D and AChE than controls (41.3% and 14.5%, respectively) at the high exposure period. When all biomarkers of individual susceptibility to pesticides were considered at the same time, the GSTT1 null allele determined higher ALA-D and AChE activities at the period of high exposure to pesticides. PON1 R allele in turn determined lower AChE activity at the low exposure period. Null genotype for both GST subclasses (GSTM1 and GSTT1) was found to be the unique independent predictor of pesticide-related symptomatology. Interestingly, sprayers were consistently underrepresented among carriers of "unfavourable" BChE variants. In conclusion, ALA-D appears to be an important biological indicator of pesticide exposure and PON1 and GSTT1 are relevant determinants of susceptibility to chronic pesticide poisoning.
authors.affiliation: Department of Legal Medicine and Toxicology, University of Granada School of Medicine, Granada, Spain. ajerez@ugr.es
authors.forename: Antonio F
authors.initials: AF
authors.lastname: Hernández
authors.forename: Olga
authors.initials: O
authors.lastname: López
authors.forename: Lourdes
authors.initials: L
authors.lastname: Rodrigo
authors.forename: Fernando
authors.initials: F
authors.lastname: Gil
authors.forename: Gloria
authors.initials: G
authors.lastname: Pena
authors.forename: José Luis
authors.initials: JL
authors.lastname: Serrano
authors.forename: Tesifón
authors.initials: T
authors.lastname: Parrón
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Alvarez
authors.forename: José Antonio
authors.initials: JA
authors.lastname: Lorente
authors.forename: Antonio
authors.initials: A
authors.lastname: Pla
mesh_terms: D000109:Acetylcholine / Q000097:blood; D000293:Adolescent; D000328:Adult; D000383:Agriculture; D043303:Aryldialkylphosphatase / Q000097:blood / Q000235:genetics; D015415:Biomarkers; D002091:Butyrylcholinesterase / Q000097:blood; D004912:Erythrocytes / Q000187:drug effects / Q000201:enzymology*; D005260:Female; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D016273:Occupational Exposure; D010575:Pesticides / Q000633:toxicity*; D011110:Polymorphism, Genetic; D000623:Porphobilinogen Synthase / Q000097:blood / Q000235:genetics
chemical_list: D015415:Biomarkers; D010575:Pesticides; D005979:Glutathione Peroxidase; D002091:Butyrylcholinesterase; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human; D000623:Porphobilinogen Synthase; D000109:Acetylcholine