title: Application of the buccal micronucleus cytome assay and analysis of PON1Gln192Arg and CYP2A6*9(-48T>G) polymorphisms in tobacco farmers.
abstract: Tobacco is a major Brazilian cash crop. Tobacco farmers apply large amounts of pesticides to control insect growth. Workers come into contact with green tobacco leaves during the tobacco harvest and absorb nicotine through the skin. In the present study, micronucleus frequency, cell death, and the frequency of basal cells were measured in tobacco farmers using the buccal micronucleus cytome assay (BMCyt), in parallel with measurement of blood butyrylcholinesterase (BChE) and nicotine levels. Polymorphisms in PONIGln192Arg and CYP2A6*9(-48T>G) were evaluated to verify the relationship between genetic susceptibility and the measured biomarkers. Peripheral blood and buccal cell samples were collected from 106 agricultural workers, at two different crop times (during pesticide application and leaf harvest), as well as 53 unexposed controls. BMCyt showed statistically significant increases in micronuclei, nuclear buds, and binucleated cells among exposed subjects in differentiated cells, and in micronuclei in basal cells. In addition, the exposed group showed higher values for condensed chromatin, karyorrhectic, pyknotic, and karyolitic cells, indicative of cell death, and an increase in the frequency of basal cells compared to the unexposed control group. A slight difference in mutagenicity using the BMCyt assay was found between the two different sampling times (pesticide application and leaf harvest), with higher micronucleus frequencies during pesticide application. Elevated cotinine levels were observed during the leaf harvest compared to the unexposed controls, while BChE level was similar among the farmers and controls. PONIGln192Arg and CYP2A6*9(-48T>G) polymorphisms were associated with DNA damage induced by pesticides and cell death.
authors: Department of Genetics and Molecular Biology, Postgraduate Program in Genetics and Molecular Biology (PPGBM), Federal University of Rio Grande do Sul (UFRGS), Porto Alegre-RS, Brazil.
authors: Fernanda Rabaioli
authors: FR
authors: Da Silva
authors: Juliana
authors: J
authors: Da Silva
authors: Emilene
authors: E
authors: Nunes
authors: Danieli
authors: D
authors: Benedetti
authors: Vivian
authors: V
authors: Kahl
authors: Paula
authors: P
authors: Rohr
authors: Marina B
authors: MB
authors: Abreu
authors: Flávia Valladão
authors: FV
authors: Thiesen
authors: Kátia
authors: K
authors: Kvitko
mesh_terms: D000383:Agriculture; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D043303:Aryldialkylphosphatase / Q000235:genetics*; D001938:Brazil; D016923:Cell Death / Q000187:drug effects; D003367:Cotinine; D065637:Cytochrome P-450 CYP2A6; D004249:DNA Damage / Q000187:drug effects*; D005819:Genetic Markers / Q000235:genetics; D006801:Humans; D015162:Micronucleus Tests; D009061:Mouth Mucosa / Q000166:cytology; D009152:Mutagenicity Tests; D009538:Nicotine / Q000032:analysis / Q000633:toxicity; D016273:Occupational Exposure / Q000009:adverse effects*; D010575:Pesticides / Q000633:toxicity*; D011110:Polymorphism, Genetic / Q000235:genetics*; D014026:Nicotiana / Q000737:chemistry / Q000633:toxicity*
chemical_list: D005819:Genetic Markers; D010575:Pesticides; D009538:Nicotine; D001189:Aryl Hydrocarbon Hydroxylases; C585710:CYP2A6 protein, human; D065637:Cytochrome P-450 CYP2A6; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human; D003367:Cotinine