CYP polymorphisms and pathological conditions related to chronic exposure to organochlorine pesticides.
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ABSTRACT:
SUBMITTER: Docea AO
PROVIDER: S-EPMC5615117 | biostudies-literature | 2017
REPOSITORIES: biostudies-literature
Publications
CYP polymorphisms and pathological conditions related to chronic exposure to organochlorine pesticides.
Docea Anca Oana AO Vassilopoulou Loukia L Fragou Domniki D Arsene Andreea Letitia AL Fenga Concettina C Kovatsi Leda L Petrakis Dimitrios D Rakitskii Valerii N VN Nosyrev Alexander E AE Izotov Boris N BN Golokhvast Kirill S KS Zakharenko Alexander M AM Vakis Antonis A Tsitsimpikou Christina C Drakoulis Nikolaos N
Toxicology reports 20170526
The association between genetic variations in the cytochrome P450 (CYP) family genes and pathological conditions related to long-term exposure to organochlorine compounds (OCs) deserves further elucidation. OCs are persistent organic pollutants with bioaccumulative and lipophilic characteristics. They can act as endocrine disruptors and perturb cellular mechanisms. Prolonged exposure to OCs has been associated with different pathological manifestations. CYP genes are responsible for transcribing ...[more]
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Project description:The aim of this study was to examine the hypothesis that organochlorine pesticides (OCPs), hexachlorobenzene (HCB), β-hexachlorocyclohexane (β-HCH), and 1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane (p,p'-DDT) and its metabolite 1,1-dichloro-2,2-bis(4-chlorophenyl)ethylene (p,p'- DDE) are ototoxic to humans. A multivariate general linear model was designed, in which the statistical relation between blood serum concentrations of HCB, β-HCH, p,p'-DDT, or p,p'-DDE at different ages (at birth, 6, 16, and 45 months) and the distortion product otoacoustic emissions (DPOAEs) was treated as multivariate outcome variables. Polychlorinated biphenyl (PCB) congeners and OCPs were strongly correlated in serum of children from our cohort. To ascertain that the association between DPOAEs at a given frequency and concentration of a pesticide is not influenced by PCBs or other OCP also present in serum, we calculated benchmark concentrations (BMCs) relating DPOAEs to a serum pesticide alone and in presence of confounding PCB-153 or other OCPs. We found that BMCs relating DPOAEs to serum pesticides are not affected by confounders. DPOAE amplitudes were associated with serum OCPs at all investigated time intervals, however, in a positive way with prenatal exposure and in a negative way with all postnatal exposures. We observed tonotopicity in the association of pesticides with amplitude of DPOAEs as its strength was frequency dependent. We conclude that exposure to OCPs in infancy at environmental concentrations may be associated with hearing deficits.
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Project description:The current study aimed to investigate temporal trends of serum organochlorine pesticide (OCP) concentrations in the general United States population, approximately 30 years after the prohibition of OCP usage, by using National Health and Nutrition Examination Survey data. The least square geometric means and percent change in OCP concentrations were calculated by a survey weighted multiple linear regression model. Over 2005-2016, OCP concentrations showed significant downward temporal trends. Females had substantially higher concentrations of β-Hexachlorocyclohexane (β-HCH), p,p'-DDE and p,p'-DDT, but lower concentrations of Hexachlorobenzene (HCB) and trans-nonachlor. In addition, females had a more rapid decrease in p,p'-DDT levels over time than males. The overall OCP concentrations increased with age, and the two oldest age groups (aged 40-59 and 60+ years) had substantially lower rates of decrease than the younger age groups (aged 12-39 years). Concentrations and declines in OCPs (except for trans-nonachlor) were higher in Mexican Americans than both non-Hispanic Whites and non-Hispanic Blacks. There is a particular need for the ongoing monitoring of these banned chemicals, and measures should be taken to mitigate the exposure of vulnerable populations, including adults aged over 60, Mexican Americans, females for β-HCH, p,p'-DDE and p,p'-DDT, and males for HCB and trans-nonachlor.
| S-EPMC8997618 | biostudies-literature
Project description:BackgroundLimited human data suggest an association of organochlorine pesticides (OCPs) with adverse effects on children's growth.ObjectiveWe evaluated the associations of OCPs with longitudinally assessed growth among peripubertal boys from a Russian cohort with high environmental OCP levels.MethodsA cohort of 499 boys enrolled in the Russian Children's Study between 2003 and 2005 at 8-9 years of age were followed prospectively for 4 years. At study entry, 350 boys had serum OCPs measured. Physical examinations were conducted at entry and annually. The longitudinal associations of serum OCPs with annual measurements of body mass index (BMI), height, and height velocity were examined by multivariate mixed-effects regression models for repeated measures, controlling for potential confounders.ResultsAmong the 350 boys with OCP measurements, median serum hexachlorobenzene (HCB), ?-hexachlorocyclohexane (?HCH), and p,p´-dichlorodiphenyldichloroethylene (p,p´-DDE) concentrations were 159 ng/g lipid, 168 ng/g lipid, and 287 ng/g lipid, respectively. Age-adjusted BMI and height z-scores generally fell within the normal range per World Health Organization standards at entry and during follow-up. However, in adjusted models, boys with higher serum HCB, ?HCH, and p,p´-DDE had significantly lower mean [95% confidence interval (CI)] BMI z-scores, by -0.84 (-1.23, -0.46), -1.32 (-1.70, -0.95), and -1.37 (-1.75, -0.98), respectively, for the highest versus lowest quintile. In addition, the highest quintile of p,p´-DDE was associated with a significantly lower mean (95% CI) height z-score, by -0.69 (-1.00, -0.39) than that of the lowest quintile.ConclusionsSerum OCP concentrations measured at 8-9 years of age were associated with reduced growth, particularly reduced BMI, during the peripubertal period, which may affect attainment of optimal adult body mass and height.
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