PMID: 

Environ Health Perspect. 2019 01 ;127(1):17005. PMID: 30648881

Abstract Title: 

High Pesticide Exposure Events and Olfactory Impairment among U.S. Farmers.

Abstract: 

BACKGROUND: Olfactory impairment (OI) is common among older adults and independently predicts all-cause mortality and the risk of several major neurodegenerative diseases. Pesticide exposure may impair olfaction, but empirical evidence is lacking.OBJECTIVE: We aimed to examine high pesticide exposure events (HPEEs) in relation to self-reported OI in participants in the Agricultural Health Study (AHS).METHODS: We conducted multivariable logistic regression to examine the associations between HPEEs reported at enrollment (1993–1997) and self-reported OI at the latest AHS follow-up (2013–2015) among 11,232 farmers, using farmers without HPEEs as the reference or unexposed group.RESULTS: A total of 1,186 (10.6%) farmers reported OI. A history of HPEEs reported at enrollment was associated with a higher likelihood of reporting OI two decades later {odds ratio [Formula: see text] [95% confidence interval (CI): 1.28, 1.73]}. In the analyses on the HPEE involving the highest exposure, the association appears to be stronger when there was a [Formula: see text] delay between HPEE and washing with soap and water [e.g., [Formula: see text] (95% CI: 1.48, 2.89) for 4-6 h vs. [Formula: see text] (95% CI: 1.11, 1.75) for [Formula: see text]]. Further, significant associations were observed both for HPEEs involving the respiratory or digestive tract [[Formula: see text] (95% CI: 1.22, 1.92)] and dermal contact [[Formula: see text] (95% CI: 1.22, 1.78)]. Finally, we found significant associations with several specific pesticides involved in the highest exposed HPEEs, including two organochlorine insecticides (DDT and lindane) and four herbicides (alachlor, metolachlor, 2,4-D, and pendimethalin). HPEEs that occurred after enrollment were also associated with OI development.CONCLUSIONS: HPEEs may cause long-lasting olfactory deficit. Future studies should confirm these findings with objectively assessed OI and also investigate potential mechanisms. https://ift.tt/36ZFyHb.

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PMID: 

Environ Int. 2019 04 ;125:161-171. Epub 2019 Feb 1. PMID: 30716576

Abstract Title: 

Plasma levels of dichlorodiphenyldichloroethene (DDE) and dichlorodiphenyltrichloroethane (DDT) and survival following breast cancer in the Carolina Breast Cancer Study.

Abstract: 

OBJECTIVES: To examine plasma levels of dichlorodiphenyldichloroethene (DDE) and dichlorodiphenyltrichloroethane (DDT) in association with survival among women with breast cancer who participated in a population-based case-control study.METHODS: Participants included 456 white and 292 black women from the Carolina Breast Cancer Study Phase I who were diagnosed with primary invasive breast cancer from 1993 to 1996, and who had available DDE/DDT and lipid measurements from blood samples obtained on average 4.1 months after diagnosis. Using the National Death Index, we identified 392 deaths (210 from breast cancer) over a median follow-up of 20.6 years. We used Cox regression to estimate covariate-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause and breast cancer-specific5-year mortality, and 20-year mortality conditional on 5-year survival, for lipid-standardized DDE and DDT levels. Associations stratified by race and estrogen receptor (ER) status were also examined.RESULTS: The highest versus lowest DDE tertile and the highest vs non-detectable DDT quantile were associated with HRs of 1.95 (95% CI = 1.31-2.92) and 1.64 (95% CI = 1.10-2.44), respectively, for 20-year conditional all-cause mortality. DDE levels above versus below the median were associated with a HR of 1.69 (95% CI = 1.06-2.68) for 20-year conditional breast cancer-specific mortality among women overall, and HRs were 2.36 (95% CI = 1.03-5.42) among black women and 1.57 (95% CI = 0.86-2.89) among white women (P = 0.42), and 3.24 (95% CI = 1.38-7.58) among women with ERtumors and 1.29 (95% CI = 0.73-2.28) among women with ERtumors (P = 0.03).CONCLUSION: Exposure to DDE/DDT may adversely impact overall and breast cancer-specific survival. DDE exposure may contribute to the racial disparities in breast cancer survival.

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PMID: 

J Natl Cancer Inst. 2019 Feb 13. Epub 2019 Feb 13. PMID: 30759253

Abstract Title: 

DDT and Breast Cancer: Prospective Study of Induction Time and Susceptibility Windows.

Abstract: 

Background: In a previous Child Health and Development Studies report, p, p'-DDT was associated with a fivefold increased risk of premenopausal (before age 50 years) breast cancer for women first exposed before puberty. Here we extend our observation to breast cancer diagnosed during early postmenopause (ages 50-54 years) to determine whether age at diagnosis modifies the interaction of DDT with age at exposure.
Methods: We conducted a second prospective, nested case-control study in the Child Health and Development Studies (153 incident breast cancer cases diagnosed at ages 50-54 years and 432 controls matched to cases on birth year). These were analyzed separately and pooled with our previous study (129 breast cancer cases diagnosed at ages 31-49 years and 129 controls matched on birth year). Blood samples were obtained during pregnancy (median age, 26 years), 1-3 days after delivery from 1959 to 1967 in Oakland, California. Serum was assayed for p, p'-DDT, o, p'-DDT, and p, p'-DDE. Odds ratios (ORs) below are given for doubling of serum p, p'-DDT. All statistical tests were two-sided.
Results: For early postmenopausal breast cancer, p, p'-DDT was associated with risk for all women (ORDDT 50-54 = 1.99, 95% CI = 1.48 to 2.67). This association was accounted for by women first exposed to DDT after infancy (ORDDT 50-54 for first exposure after infancy = 2.83, 95% CI = 1.96 to 4.10 vs ORDDT 50-54 for first exposure during infancy = 0.56, 95% CI = 0.26 to 1.19; Pinteraction DDT x age at first exposure = .01). In contrast, for premenopausal breast cancer, p, p'-DDT was associated with risk among women first exposed during infancy through puberty, but notafter (ORDDT<50 for first exposure during infancy = 3.70, 95% CI = 1.22 to 11.26, Pinteraction DDT x age at first exposure x age at diagnosis = .03).
Conclusions: p, p'-DDT was associated with breast cancer through age 54 years. Risk depended on timing of first exposure and diagnosis age, suggesting susceptibility windows and an induction period beginning in early life. DDT appears to be an endocrine disruptor with responsive breast targets from in utero to menopause.

PMID: 

Reprod Toxicol. 2019 Feb 26. Epub 2019 Feb 26. PMID: 30822522

Abstract Title: 

DDT exposure during pregnancy and DNA methylation alterations in female offspring in the Child Health and Development Study.

Abstract: 

Studies measuring dichlorodiphenyltrichloroethane (DDT) exposure during key windows of susceptibility including the intrauterine period suggest that DDT exposure is associated with breast cancer risk. We hypothesized that prenatal DDT exposure is associated with DNA methylation. Using prospective data from 316 daughters in the Child Health and Development Study, we examined the association between prenatal exposure to DDTs and DNA methylation in blood collected in midlife (mean age: 49 years). To identify differentially methylated regions (DMRs) associated with markers of DDTs (p,p'-DDT and the primary metabolite of p,p'-DDT, p,p'-DDE, and o,p'-DDT, the primary constituents of technical DDT), we measured methylation in 30 genes important to breast cancer. We observed DDT DMRs in three genes, CCDC85A, CYP1A1 and ZFPM2, each of which has been previously implicated in pubertal development and breast cancer susceptibility. These findings suggest prenatal DDT exposure may have life-long consequence through alteration in genes relevant to breast cancer.

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PMID: 

J Cell Biochem. 2019 Sep ;120(9):14847-14859. Epub 2019 Apr 22. PMID: 31009110

Abstract Title: 

Organochlorine and organophosphorus pesticides and bladder cancer: A case-control study.

Abstract: 

BACKGROUND: Exposure to pesticides is associated with an increase in the incidence of cancer. We aimed to investigate the association of serum organochlorine pesticides (OCPs) and organophosphorus pesticides (OPs) levels and GSTM1/GSTT1 gene polymorphism with bladder cancer (BC).METHODS: This study was performed on 57 patients with BC and 30 controls (C). Acetylcholinesterase (AChE) activity, arylesterase activity of paraoxonase-1 (ARE), total antioxidant capacity (TAC), and malondialdehyde (MDA) levels were determined in serums of all participants. Genomic DNA was extracted using the salting out method and GSTM1/GSTT1 gene polymorphisms were examined by multiplex polymerase chain reaction assay. Measurement of OCPs (α-hexachlorocyclohexane [α-HCH], β-HCH, γ-HCH, 2,4-dichlorodiphenyltrichloroethane [2,4-DDT], 4,4-DDT, 2,4- dichlorodiphenyldichloroethylene [2,4-DDE], and 4,4-DDE) in serum was carried out using an FID-equipped gas-chromatography system.RESULTS: AChE activity was significantly lower, ARE activity and TAC were declined but it was not statistically significant, however, α-HCH, γ-HCH, 4,4-DDE, 2,4-DDT, and 4,4-DDT pesticides, and MDA were significantly higher in BC patients compared with the control subjects. Also, a positive correlation was found between the number of smoked cigarettes andthe years of smoking with BC development. There was no association between GSTM1/GSTT1 gene polymorphisms and OCPs in BC patients.CONCLUSION: Due to the higher levels of some OCPs in the BC patients, along with the reduction in AChE activity and increased MDA levels, it may be concluded that OCPs and OPs play an important role in the induction of BC in southeastern Iran.

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PMID: 

Environ Epigenet. 2019 Apr ;5(2):dvz008. Epub 2019 May 27. PMID: 31186947

Abstract Title: 

Sperm epimutation biomarkers of obesity and pathologies following DDT induced epigenetic transgenerational inheritance of disease.

Abstract: 

Dichlorodiphenyltrichloroethane (DDT) has previously been shown to promote the epigenetic transgenerational inheritance of adult onset disease in rats. The current study investigated the potential that sperm epimutation biomarkers can be used to identify ancestral induced transgenerational obesity and associated pathologies. Gestating F0 generational female rats were transiently exposed to DDT during fetal gonadal sex determination, and the incidence of adult-onset pathologies was assessed in the subsequent F1, F2, and F3 generations. In addition, sperm differential DNA methylation regions (DMRs) that were associated with specific pathologies in the transgenerational F3 generation males were investigated. There was an increase of testis disease and early-onset puberty in the F2 generation DDT lineage males. The F3 generation males and females had significant increases in the incidence of obesity and multiple disease. The F3 generation DDT males also had significant increases in testis disease, prostate disease, and late onset puberty. The F3 generation DDT females had increases in ovarian and kidney disease. Epigenetic alterations of the germline are required for the transgenerational inheritance of pathology. Therefore, the F3 generation sperm was collected to examine DMRs for the ancestrally exposed DDT male population. Unique sets of DMRs were associated with late onset puberty, prostate disease, kidney disease, testis disease, obesity, and multiple disease pathologies. Gene associations with the DMR were also identified. The epigenetic DMR signatures identified for these pathologies provide potential biomarkers for transgenerationally inherited disease susceptibility.

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PMID: 

Environ Toxicol Pharmacol. 2019 Nov ;72:103263. Epub 2019 Sep 12. PMID: 31542660

Abstract Title: 

The organochlorine pesticides pentachlorophenol and dichlorodiphenyltrichloroethane increase secretion and production of interleukin 6 by human immune cells.

Abstract: 

The environmental contaminants pentachlorophenol (PCP) and 4, 4'-dichlorodiphenyltrichloroethane (DDT) are detected in some human blood samples at levels as high as 5μM (PCP) and 260 nM (DDT). Several cancers are associated with exposures to these contaminants. IL-6 is a pro-inflammatory cytokine that when dysregulated stimulates inflammatory diseases and tumor progression. Immune cells exposed to PCP at 0.05-5 μM and DDT at 0.025-2.5 μM showed increased secretion of IL-6 when the cell preparations contained either T lymphocytes or monocytes. Increased IL-6 secretion was due to PCP and DDT induced cellular production of the cytokine and was dependent on MAP kinase signaling pathways (in the case of PCP). Compound-induced increases in IL-6 production were in part due to increases in either the transcription of and/or stability of its mRNA. Thus, both PCP and DDT have the potential to produce chronic inflammation by stimulating production of IL-6 by immune cells.

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PMID: 

Int J Hyg Environ Health. 2019 Nov 8. Epub 2019 Nov 8. PMID: 31708466

Abstract Title: 

Multiple pesticides in mothers' hair samples and children's measurements at birth: Results from the French national birth cohort (ELFE).

Abstract: 

BACKGROUND: A growing body of studies now suggests that the general population is continuously and ubiquitously exposed to numerous pesticides. However, studies investigating the possible role of environmental exposure to pesticides on fetal growth have focused on a limited set of substances, despite the hundreds of modern pesticides currently available.AIM: To explore the relation between maternal hair concentrations of 64 pesticides and metabolites and their newborns' measurements at birth, with data from the ELFE French nationwide birth cohort.METHODS: We measured 64 compounds (10-100% detection) in bundles of hair 9 cm long collected at birth from 311 women who gave birth in France in 2011. We assessed their associations with birth weight, length, and head circumference, adjusted for potential confounders, and used elastic net regularization to simultaneously select the strongest predictors of measurements at birth. Selected variables were multiply imputed for missing values, and unpenalized estimators were assessed by standard linear regression.RESULTS: We observed statistically significant associations between maternal hair concentrations of seven pesticides or pesticide metabolites and birth measurements (weight: fipronil sulfone; length: TCPy, bitertanol, DEP, and isoproturon; head circumference: tebuconazole and prochloraz). Analyses restricted to boys identified 12 additional compounds: 8 independently associated with birth weight (3Me4NP, DCPMU, DMST, fipronil, mecoprop, propoxur, fenhexamid, and thiabendazole), 2 with birth length (dieldrin andβ-endosulfan), and 6 with head circumference (β-endosulfan, β-HCH, fenuron, DCPMU, propoxur, and thiabendazole).CONCLUSION: Our results suggest that prenatal exposure to 19 pesticides or metabolites from various chemical families may influence measurements at birth. As with any exploratory research findings, results should be interpreted cautiously, until they are replicated or verified by further epidemiological or mechanistic studies.

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PMID: 

Reprod Toxicol. 2019 Nov 8. Epub 2019 Nov 8. PMID: 31711904

Abstract Title: 

In Utero DDT Exposure and Breast Density Before Age 50.

Abstract: 

Prior studies in the Child Health and Development Studies (CHDS) found in utero exposure to the pesticide, dichlorodiphenyltrichloroethane (DDT), increased breast cancer risk by age 52. Mammographic density is considered a primary risk factor for breast cancer. We conducted a study of 309 daughters from the CHDS to examine in utero DDT exposure and mammographic density in midlife. Among daughters with high (>75th percentile) exposure to p,p'-Dichlorodiphenyldichloroethylene (DDE), p,p'-DDT was significantly correlated with increased dense area and percent density regardless of her body mass in midlife. In the subset of women with lower (

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PMID: 

World J Gastroenterol. 2007 Jan 14 ;13(2):250-6. PMID: 17226904

Abstract Title: 

Antiproliferation and apoptosis induction of paeonol in HepG2 cells.

Abstract: 

AIM: To investigate the antiproliferative effect of paeonol (Pae) used alone or in combination with chemotherapeutic agents [cisplatin (CDDP), doxorubicin (DOX) and 5-fluorouracil (5-FU)] on human hepatoma cell line HepG2 and the possible mechanisms.METHODS: The cytotoxic effect of drugs on HepG2 cells was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Morphologic changes were observed by acridine orange (AO) fluorescence staining. Cell cycle and apoptosis rate were detected by flow cytometry (FCM). Drug-drug interactions were analyzed by the coefficient of drug interaction (CDI).RESULTS: Pae (7.81-250 mg/L) had an inhibitory effect on the proliferation of HepG2 cells in a dose-dependent manner, with the IC50 value of (104.77 +/- 7.28) mg/L. AO fluorescence staining and FCM assays showed that Pae induced apoptosis and arrested cell cycle at S phase in HepG2 cells. Further, different extent synergisms were observed when Pae (15.63, 31.25, 62.5 mg/L) was combined with CDDP (0.31-2.5 mg/L), DOX (0.16-1.25 mg/L), or 5-FU (12.5-100 mg/L) at appropriate concentrations. The IC50 value of the three drugs decreased dramatically when combined with Pae (P

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