Modified CDKN2B (p15) and CDKN2A (p16) DNA methylation profiles in urban pesticide applicators

Herrera-Moreno, José Francisco; Medina-Díaz, Irma Martha; Bernal-Hernández, Yael Yvette; Ramos, Kenneth S.; Alvarado-Cruz, Isabel; Quintanilla‐Vega, Betzabet; González-Arias, Cyndia Azucena; Barrón-Vivanco, Briscia Socorro; Rojas-García, Aurora Elizabeth

doi:10.1007/s11356-019-04658-5

Cited by 15 publications

(10 citation statements)

References 82 publications

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“…Regarding the DNA methylation profile, our results showed an increase in %5mC in the 5 ′ UTR region of the CDKN2B gene in indigenous farmers compared to the non-farmers; conversely, there were not significant differences between study groups for CDKN2A gene methylation. Contrary to our results, Herrera-Moreno et al 10 reported a decrease in %5mC in the CDKN2B gene for groups occupationally exposed to pesticides (urban sprayers) in comparison to a reference group. In contrast with our results, Herrera-Moreno et al 10 found higher methylation in the CDKN2A gene in urban sprayers with moderate exposure to pesticides with respect to a reference group.…”

Section: Discussioncontrasting

confidence: 99%

“…Contrary to our results, Herrera-Moreno et al 10 reported a decrease in %5mC in the CDKN2B gene for groups occupationally exposed to pesticides (urban sprayers) in comparison to a reference group. In contrast with our results, Herrera-Moreno et al 10 found higher methylation in the CDKN2A gene in urban sprayers with moderate exposure to pesticides with respect to a reference group. Based on these differences in the effect of xenobiotics on gene-specific DNA methylation profiles, studies have reported that these variations may occur depending on the compound or mixture of compounds to which the population is exposed; time and intensity of exposure, as well as other factors such as race and ethnicity.…”

Section: Discussioncontrasting

confidence: 99%

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Methylation patterns of the CDKN2B and CDKN2A genes in an indigenous population exposed to pesticides

et al. 2022

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The INK4 -ARF locus includes the CDKN2B and CDKN2A genes and is functionally relevant in the regulation of both cell proliferation and senescence. Studies have reported modifications of DNA methylation in this locus by exposure to environmental contaminants including pesticides; however, until now, specific methylation profiles have not been reported in genetically conserved populations exposed to occupational pesticides. The aim of this study was to determine the methylation profiles of the CDKN2B and CDKN2A genes in a genetically conserved population exposed to pesticides. A cross-sectional and analytical study was carried out in 190 Huichol indigenous persons. Information related to pesticide exposure, diet and other variables were obtained through the use of a structured questionnaire. Blood and urine samples were collected for methylation test and dialkylphosphates (DAP) determination, respectively. DNA methylation was measured by the pyrosequencing of bisulfite-treated DNA and DAP concentrations by gas chromatography-tandem mass spectrometry (GC/MS). The most frequent metabolite in the population was dimethylthiophosphate. The farmer group presented a higher methylation percentage of CDKN2B than the non-farmer group, but no differences in CDKN2A were observed between groups. A positive correlation between methylation of CpG site 3 of CDKN2B and time working in the field was observed in the farmer group. An association between methylation percentage of CDKN2B and age was also observed in the non-farmer group. These results suggest that pesticide exposure and exposure time in Huichol indigenous individuals could modify the methylation pattern of the CDKN2B gene.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussioncontrasting

confidence: 99%

Methylation patterns of the CDKN2B and CDKN2A genes in an indigenous population exposed to pesticides

et al. 2022

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“…57 Some of our previous studies reported the association between fiber intake and methylation pattern in both global sequences (LINE-1) and specific genes. 44,58 Although we did not find data that explain a possible mechanism by which dietary fiber intake produces changes in specific or global methylation pattern, it has been reported that the consumption of dietary fiber is related to reduction in the risk of colorectal cancer. 59 On the other hand, vitamin intake has been associated with genome-wide methylation profile in several studies.…”

Section: ■ Discussioncontrasting

confidence: 68%

“…Some studies have evaluated gene-specific DNA methylation in populations exposed to pesticides. ,,, Specifically, Howard et al identified changes in DNA methylation at 36 CpG sites, located in or near to 72 genes, in farmworkers compared with nonfarmworkers. Lee et al observed a hypomethylation in the Alu assay for men and global DNA hypermethylation in LINE-1 for women in a population exposed to persistent organic pollutant, including organochlorine pesticides.…”

Section: Discussionmentioning

confidence: 99%

Pesticide Exposure Modifies DNA Methylation of Coding Region of WRAP53α, an Antisense Sequence of p53, in a Mexican Population

Paredes-Céspedes

Herrera-Moreno

Bernal-Hernández

et al. 2019

Chem. Res. Toxicol.

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The influence of pesticide exposure in alteration of DNA methylation patterns of specific genes is still limited, specifically in natural antisense transcripts (NAT), such as the WRAP53α gene. The aim of this study was to determine the methylation of the WRAP53α gene in mestizo and indigenous populations as well as its relationship with internal (age, sex, and body mass index) and external factors (pesticide exposure and micronutrient intake). A crosssectional study was conducted including 91 mestizo individuals without occupational exposure to pesticides, 164 mestizo urban sprayers and 189 indigenous persons without occupational exposure to pesticides. Acute pesticide exposure was evaluated by measurement of urinary dialkylphosphate (DAP) concentration by gas chromatograph coupled to a mass spectrometer. Anthropometric characteristics, unhealthy habits, and chronic pesticide exposure were assessed using a structured questionnaire. The frequency of macro-and micronutrient intake was determined using SNUT software. DNA methylation of the WRAP53α gene was determined by pyrosequencing of bisulfite-modified DNA. The mestizo sprayers group had the higher values of %5mC. In addition, this group had the most DAP urinary concentration with respect to the indigenous and reference groups. Bivariate analysis showed an association between %5mC of the WRAP53α gene with micronutrient intake and pesticide exposure in mestizo sprayers, whereas changes in %5mC of the WRAP53α gene was associated with body mass index in the indigenous group. These data suggest that the %5mC of the WRAP53α gene can be influenced by pesticide exposure and ethnicity in the study population, and changes in the WRAP53α gene might cause an important cell process disturbance.

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“…Significant impacts upon gene expression were only identified for seven of these, which may suggest a broader impact upon the epigenome than locus-specific modulation of gene expression. In 2019, Herrera-Moreno et al ( 67 ) looked for methylation changes within the 5′UTR region of the CDKN2B gene and the promoter of Cyclin Dependent Kinase Inhibitor 2A ( CDKN2A) in Mexican workers exposed to pesticides. CDKN2B hypomethylation was observed in exposed individuals, with a signification association between methylation and exposure levels, while hypermethylation of the CDKN2A promoter was observed in moderately-exposed individuals.…”

Section: Resultsmentioning

confidence: 99%

Toxicomethylomics revisited: A state-of-the-science review about DNA methylation modifications in blood cells from workers exposed to toxic agents

Jiménez-Garza

Ghosh

Barrow

et al. 2023

Front. Public Health

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IntroductionEpigenetic marks have been proposed as early changes, at the subcellular level, in disease development. To find more specific biomarkers of effect in occupational exposures to toxicants, DNA methylation studies in peripheral blood cells have been performed. The goal of this review is to summarize and contrast findings about DNA methylation in blood cells from workers exposed to toxicants.MethodsA literature search was performed using PubMed and Web of Science. After first screening, we discarded all studies performed in vitro and in experimental animals, as well as those performed in other cell types other than peripheral blood cells. Results: 116 original research papers met the established criteria, published from 2007 to 2022. The most frequent investigated exposures/labor group were for benzene (18.9%) polycyclic aromatic hydrocarbons (15.5%), particulate matter (10.3%), lead (8.6%), pesticides (7.7%), radiation (4.3%), volatile organic compound mixtures (4.3%), welding fumes (3.4%) chromium (2.5%), toluene (2.5%), firefighters (2.5%), coal (1.7%), hairdressers (1.7%), nanoparticles (1.7%), vinyl chloride (1.7%), and others. Few longitudinal studies have been performed, as well as few of them have explored mitochondrial DNA methylation. Methylation platforms have evolved from analysis in repetitive elements (global methylation), gene-specific promoter methylation, to epigenome-wide studies. The most reported observations were global hypomethylation as well as promoter hypermethylation in exposed groups compared to controls, while methylation at DNA repair/oncogenes genes were the most studied; studies from genome-wide studies detect differentially methylated regions, which could be either hypo or hypermethylated.DiscussionSome evidence from longitudinal studies suggest that modifications observed in cross-sectional designs may be transitory; then, we cannot say that DNA methylation changes are predictive of disease development due to those exposures.ConclusionDue to the heterogeneity in the genes studied, and scarcity of longitudinal studies, we are far away from considering DNA methylation changes as biomarkers of effect in occupational exposures, and nor can we establish a clear functional or pathological correlate for those epigenetic modifications associated with the studied exposures.

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Modified CDKN2B (p15) and CDKN2A (p16) DNA methylation profiles in urban pesticide applicators

Cited by 15 publications

References 82 publications

Methylation patterns of the CDKN2B and CDKN2A genes in an indigenous population exposed to pesticides

Methylation patterns of the CDKN2B and CDKN2A genes in an indigenous population exposed to pesticides

Pesticide Exposure Modifies DNA Methylation of Coding Region of WRAP53α, an Antisense Sequence of p53, in a Mexican Population

Toxicomethylomics revisited: A state-of-the-science review about DNA methylation modifications in blood cells from workers exposed to toxic agents

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