Hematological indices as indicators of inflammation induced by exposure to pesticides.

Pesticide toxicity, both acute and chronic, is a global public health concern. Pesticides are involved in abnormal inflammatory responses by interfering with the normal physiology and metabolic status of cells. In this regard, inflammatory indices aggregate index of systemic inflammation (AISI), monocyte-to-high-density lipoprotein ratio, monocyte-to-lymphocyte ratio (MLR), neutrophil-to-lymphocyte platelet ratio (NLPR), neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, systemic immune inflammation index, and systemic inflammation response index (SIRI) have been used as predictive markers of inflammatory status in several diseases and also in acute poisoning events. This study aimed to determine systemic inflammation indices and their relationship with pesticide exposure from urban sprayers in 302 individuals categorized into three groups (reference group and moderate and high exposure groups). The data suggest that the AISI, MLR, NLPR, and SIRI indices were significantly higher in the exposed groups compared with the reference group. In conclusion, this study proposes that inflammation indices warrant further attention in order to assess their value as early biomarkers of acute and chronic pesticide intoxication.

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

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.

Relationship between butyrylcholinesterase activity and lipid parameters in workers occupationally exposed to pesticides.

Exposure to organophosphate pesticides (OP) has been associated with the inhibition of cholinesterase enzymatic activity, such as butyrylcholinesterase (BuChE). Changes in BuChE activity have been associated with obesity, diabetes, hyperthyroidism, and metabolic syndrome. However, few studies have evaluated the effects of pesticides on both BuChE and lipid parameters. The aim of this study was to evaluate lipid parameters in urban sprayers and their association with BuChE activity. An analytical cross-sectional study was conducted in workers exposed to pesticides. The pesticide exposures were evaluated by the measurement of urinary dialkylphosphates. BuChE activity was determined spectrophotometrically in serum, and biochemical parameters were determined at a certified laboratory. Information regarding general characteristics, lifestyle, and other aspects was obtained from a structured questionnaire. The results showed variations in glucose, cholesterol, albumin, atherogenic index, creatinine, LDL, VLDL, triglycerides, and total lipids according to the level of exposure to pesticides in individuals with overweight and obesity. Furthermore, positive correlations between BuChE activity and lipid parameters were observed; these effects were associated with the body mass index. More studies are needed in human population to better elucidate the role of BuChE in lipid metabolism.

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

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.

Micronucleus frequency is correlated with antioxidant enzyme levels in workers occupationally exposed to pesticides.

Oxidative stress can cause DNA damage leading to nuclear anomalies such as micronuclei (MN). Antioxidant enzymes involved in protection against intracellular oxidative stress include glutathione peroxidase (GPx), glutathione reductase (GR), superoxide dismutase (SOD), and catalase (CAT). Pesticide exposure induces oxidative stress and alters antioxidant defense mechanisms, including detoxification and scavenger enzymes. The aim of this study was to evaluate MN frequency in workers occupationally exposed to pesticides and their relationship with antioxidant enzyme activities. A cross-sectional study was conducted in 201 individuals, some of whom were dedicated to the spraying of pesticides. The cytokinesis-block micronucleus (CBMN) assay was conducted, and the activities of GPx, GR, SOD, and CAT were determined. The geometric mean (GM) of MN was 5.4 (1-26 MN). The GM for the antioxidant enzymes was 198.68 U/mL for GPx, 38.96 U/g Hb for GR, 94.78 U/mL for SOD, and 69.77 U/g Hb for CAT. There was a lower MN frequency in males than that in females, and a higher nuclear index. In addition, age affected MN frequency. There was a negative correlation between MN frequency and GPx activity, but a positive one between MN frequency and GR activity. These findings suggest the involvement of GPx in MN frequency.

Aberrant promoter methylation in genes related to hematopoietic malignancy in workers exposed to a VOC mixture.

Occupational exposure to volatile organic compounds (VOCs) may cause hematopoietic malignancy, either by single exposure to benzene or possibly due to a concomitant exposure to several VOCs. Since oxidative stress, inflammation and DNA repair pathways are closely involved in cancer development, the effect of VOC exposure on expression of proteins involved in these pathways has been studied, but epigenetic changes have not been well described. Here, DNA methylation status following occupational exposure to a VOC mixture was assessed by bisulfite sequencing of the promoter regions of seven genes involved in the mentioned pathways. Peripheral blood samples and individual-level VOC exposure data were obtained from healthy leather shoe factory workers (LS, n=40) and gas station attendants (GS, n=36), as well as a reference group of university employees (C, n=66). Exposure levels for acetone, ethylbenzene, methyl ethyl ketone, n-hexane, toluene and xylene were higher in LS (p<0.001); benzene and methyl acetate levels were higher in GS (p<0.001). TOP2A, SOD1, and TNF-α promoter methylation status was increased in LS (p<0.05). In LS, we also found significant correlations between GSTP1 promoter methylation and both iNOS (r=0.37, p=0.008) and COX-2 (r=-0.38, p=0.007) methylation. In exposed groups, ethylbenzene exposure levels showed a significant correlation with TOP2A methylation (ß=0.33). Our results show early, toxic effects at the epigenetic level caused by occupational exposure to high levels of a VOC mixture. These subcellular modifications may represent the initial mechanism of toxicity leading to hematopoietic malignancy, possibly due to a synergistic, hematotoxic effect of VOC mixtures.

Human papilloma virus genotypes in women from Nayarit, Mexico, with squamous intraepithelial lesions and cervical cancer.

OBJECTIVE: In Mexico cervical cancer (CC) is the most common cause of death from neoplasia in women. Study aimed to analyze the current distribution of Human papillomavirus (HPV) types in women from Nayarit, Mexico, with Squamous intraepithelial lesions (SIL) and Cervical cancer (CC). METHODOLOGY: Between January 2011 and July 2013, cervical samples were collected from female residents of the Mexican state of Nayarit and were analyzed by means of a LINEAR ARRAY® HPV genotyping test. Data analyses were performed using Stata ver. 8.0 statistical software. RESULTS: Of the samples analyzed, 91.2%, HPV DNA was detected. Of these positive samples, 82% were High-risk (HR) viral types. The most prevalent HPV genotypes identified were 16, 58, 31, 18, and 70. Forty two percent of participants had a single infection, while 23 and 26% of participants were infected with two or more HPV genotypes, respectively. HPV 16 was the most prevalent genotype identified and was frequently present as a co-infection with HPV types 18, 51, 52, 59, 66, or 70. CONCLUSION: Women <20 years of age were most often infected with HPV, and the HPV Quadrivalent vaccine (types 16, 18, 6, and 11), currently available in Mexico, no confers protection against a subset of the HPV genotypes identified in the present study (58, 31, 70, and 35). Thus, it is important evaluate the geographical distribution of specific HPV genotypes in all health of center across Mexico in order to implement a successful vaccination program and to diagnose CC in its early stages.

CYP2E1 epigenetic regulation in chronic, low-level toluene exposure: Relationship with oxidative stress and smoking habit.

BACKGROUND: CYP2E1 is a versatile phase I drug-metabolizing enzyme responsible for the biotransformation of most volatile organic compounds, including toluene. Human toluene exposure increases CYP2E1 mRNA and modifies its activity in leucocytes; however, epigenetic implications of this interaction have not been investigated. GOAL: To determine promoter methylation of CYP2E1 and other genes known to be affected by toluene exposure. METHODS: We obtained venous blood from 24 tannery workers exposed to toluene (mean levels: 10.86+/-7mg/m(3)) and 24 administrative workers (reference group, mean levels 0.21+/-0.02mg/m(3)) all of them from the city of León, Guanajuato, México. After DNA extraction and bisulfite treatment, we performed PCR-pyrosequencing in order to measure methylation levels at promoter region of 13 genes. RESULTS: In exposed group we found significant correlations between toluene airborne levels and CYP2E1 promoter methylation (r=-.36, p<0.05), as well as for IL6 promoter methylation levels (r=.44, p<0.05). Moreover, CYP2E1 promoter methylation levels where higher in toluene-exposed smokers compared to nonsmokers (p=0.009). We also observed significant correlations for CYP2E1 promoter methylation with GSTP1 and SOD1 promoter methylation levels (r=-.37, p<0.05 and r=-.34, p<0.05 respectively). CONCLUSION: These results highlight the importance of considering CYP2E1 epigenetic modifications, as well as its interactions with other genes, as key factors for unraveling the sub cellular mechanisms of toxicity exerted by oxidative stress, which can initiate disease process in chronic, low-level toluene exposure. People co-exposed to toluene and tobacco smoke are in higher risk due to a possible CYP2E1 repression.

Morbidity of breast cancer and cervico-uterine cancer in women from the occidental region of Mexico.

BACKGROUND: The incidences of breast cancer (BC) and cervico-uterine cancer (CC) vary widely from country to country. In Mexico, BC mortality has doubled in the last 20 years to become the second leading cause of death for women aged 30 to 54 years. CC is the most common cause of death from neoplasia in women over 25 years old. In 2006, the state of Nayarit had one of the highest mortality rates for these types of cancers in Mexico. OBJECTIVE: To analyze and characterize the current demographics and morbidities associated with BC and CC in the state of Nayarit. MATERIAL AND METHODS: In this retrospective study, the clinical histories of patients who were diagnosed with BC or CC at the State Cancer Center from January 2006 to December 2010 were analyzed. RESULTS: A total of 406 patients with BC and 328 patients with CC were registered. The most common clinical stage for both cancer types was IIB. The municipalities of San Pedro Lagunillas and El Nayar presented the highest prevalences of BC and CC, respectively. CONCLUISION: Our results suggest that women living in poorer and more marginalized regions have a higher possibility of developing BC and CC. Because BC and CC are preventable and treatable in their early stages, demographic information from population records for these cancers is helpful in determining the incidence rates and patterns and improving decision-making processes.