TY - JOUR
T1 - Modified CDKN2B (p15) and CDKN2A (p16) DNA methylation profiles in urban pesticide applicators
AU - Herrera-Moreno, José Francisco
AU - Medina-Díaz, Irma Martha
AU - Bernal-Hernández, Yael Yvette
AU - Ramos, Kenneth S.
AU - Alvarado-Cruz, Isabel
AU - Quintanilla-Vega, Betzabet
AU - González-Arias, Cyndia Azucena
AU - Barrón-Vivanco, Briscia Socorro
AU - Rojas-García, Aurora Elizabeth
N1 - Publisher Copyright:
© 2019, Springer-Verlag GmbH Germany, part of Springer Nature.
PY - 2019/1/1
Y1 - 2019/1/1
N2 - Gene-specific changes in DNA methylation by pesticides in occupationally exposed populations have not been studied extensively. Of particular concern are changes in the methylation profile of tumor-suppressor, such as CDKN2B and CDKN2A, genes involved in oncogenesis. The aim of this study was to evaluate the methylation profiles of CDKN2B and CDKN2A genes in urban pesticide applicators and their relationship with occupational exposure to pesticides. A cross-sectional study was conducted in 186 urban pesticide applicators (categorized as high or moderate exposures) and 102 participants without documented occupational exposures to pesticides. Acute and chronic pesticide exposures were evaluated by direct measurement of urinary dialkylphosphates, organophosphate metabolites, and a structured questionnaire, respectively. Anthropometric characteristics, diet, clinical histories, and other variables were estimated through a validated self-reported survey. DNA methylation was determined by pyrosequencing of bisulfite-treated DNA. Decreased DNA methylation of the CDKN2B gene was observed in pesticide-exposed groups compared to the non-exposed group. In addition, increased methylation of the CDKN2A promoter was observed in the moderate-exposure group compared to the non-exposed group. Bivariate analysis showed an association between CDKN2B methylation and pesticide exposure, general characteristics, smoking status, and micronutrients, while changes in CDKN2A methylation were associated with pesticide exposure, sex, educational level, body mass index, smoking status, supplement intake, clinical parameters, and caffeine consumption. These data suggest that pesticide exposure modifies the methylation pattern of CDKN2B and CDKN2A genes and raise important questions about the role that these changes may play in the regulation of cell cycle activities, senescence, and aging.
AB - Gene-specific changes in DNA methylation by pesticides in occupationally exposed populations have not been studied extensively. Of particular concern are changes in the methylation profile of tumor-suppressor, such as CDKN2B and CDKN2A, genes involved in oncogenesis. The aim of this study was to evaluate the methylation profiles of CDKN2B and CDKN2A genes in urban pesticide applicators and their relationship with occupational exposure to pesticides. A cross-sectional study was conducted in 186 urban pesticide applicators (categorized as high or moderate exposures) and 102 participants without documented occupational exposures to pesticides. Acute and chronic pesticide exposures were evaluated by direct measurement of urinary dialkylphosphates, organophosphate metabolites, and a structured questionnaire, respectively. Anthropometric characteristics, diet, clinical histories, and other variables were estimated through a validated self-reported survey. DNA methylation was determined by pyrosequencing of bisulfite-treated DNA. Decreased DNA methylation of the CDKN2B gene was observed in pesticide-exposed groups compared to the non-exposed group. In addition, increased methylation of the CDKN2A promoter was observed in the moderate-exposure group compared to the non-exposed group. Bivariate analysis showed an association between CDKN2B methylation and pesticide exposure, general characteristics, smoking status, and micronutrients, while changes in CDKN2A methylation were associated with pesticide exposure, sex, educational level, body mass index, smoking status, supplement intake, clinical parameters, and caffeine consumption. These data suggest that pesticide exposure modifies the methylation pattern of CDKN2B and CDKN2A genes and raise important questions about the role that these changes may play in the regulation of cell cycle activities, senescence, and aging.
KW - CDKN2A
KW - CDKN2B
KW - Gene-specific methylation
KW - Pesticides
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U2 - 10.1007/s11356-019-04658-5
DO - 10.1007/s11356-019-04658-5
M3 - Article
C2 - 30924039
AN - SCOPUS:85065163325
SN - 0944-1344
JO - Environmental Science and Pollution Research
JF - Environmental Science and Pollution Research
ER -