The dioxin-like pollutant PCB 126 (3,3',4,4',5-pentachlorobiphenyl) affects risk factors for cardiovascular disease in female rats

Epidemiological studies suggest that exposure to persistent organic pollutants such as organochlorines might induce cardiovascular disorders and diabetes. Some of these organochlorines, such as dioxins and some dioxin-like PCBs, have been characterised as anti-estrogenic due to their inhibition of estrogenic-induced responses. In the present pilot study, 40 female rats were subjected to either exposure to the dioxin-like 3,3′,4,4′,5-pentachlorobiphenyl (PCB 126) or vehicle, as well as ovariectomy (OVX) or sham operation in a 2×2 factorial design over 12 weeks to explore potential interactions between estrogen status and PCB 126 exposure on cardiovascular risk factors.

PCB 126 increased heart weight and serum cholesterol levels in both groups. PCB 126 increased blood pressure in the sham-operated animals only.

In conclusion, PCB 126 exposure in female rats resulted in effects on cardiovascular risk factors, such as serum cholesterol, blood pressure, and heart weight. Of these effects of PCB 126, the increase in blood pressure was dependent on estrogen status.     

Serum organochlorine levels and history of lactation in Egypt

We conducted a study in Egypt to assess the determinants of organochlorine serum levels among premenopausal women and the risk of premenopausal breast cancer for women with high organochlorine serum levels. We included 69 breast cancer patients and 53 controls consisting of visitors to the hospitals of the cancer patients. We found low levels of dichlorodiphenyldichloroethylene (DDE), total dichlorodiphenyltrichloroethane, and beta-hexacholorhexane (beta-HCH) in most subjects. Mean DDE levels were 12.7 +/- 20.3 ppb for cases and 16.6 +/- 30.1 ppb for controls (P = 0.60); beta-HCH levels were 2.1 +/- 3.8 ppb for patients and 2.1 +/- 3.9 ppb for controls (P = 0.71). Interestingly, subjects with low levels had breast fed their children for an average period of 18 months. Women with no lactation history had much higher organochlorine levels than women who breast fed (P = 0.002 for DDE). Younger age, older age at first childbirth, and shorter duration of breast feeding were significant predictors of higher levels of serum DDE levels. Younger age, older age at first childbirth, and higher body mass index were significant predictors of higher beta-HCH levels. This study suggests that organochlorine serum levels in Egyptian women are quite low, but indicates an effect of breast feeding in eliminating organochlorines, which would imply exposure to children. Organochlorine serum level was not a risk factor of breast cancer in this population.     

Decreased survival in pancreatic cancer patients with high concentrations of organochlorines in adipose tissue

We analysed adipose tissue concentrations of persistent organic pollutants (POPs) in 21 cases with exocrine pancreatic cancer. The comparison group consisted of 59 subjects. Significantly increased concentrations of polychlorinated biphenyls (PCBs), hexachlorobenzene (HCB), sum of chlordanes and polybrominated diphenylethers (PBDEs) were found in the cases. For 1,1,-dichloro-2,2-bis(p-chlorophenyl)-ethylene (p,p'-DDE) no significant difference was seen. For PCBs no odds ratio (OR) could be calculated since all cases had concentration>median in controls used as a cut-off. HCB yielded OR=53.0, 95% confidence interval (CI)=4.64-605 and sum of chlordanes OR=18.4, 95% CI=2.71-124 whereas OR was not significantly increased for p,p'-DDE or PBDEs. Body mass index (BMI) at the time of tissue sampling was significantly lower for the cases. This might have influenced the results. Using BMI one year previously or decreasing the concentrations of POPs with the same percentage as weight loss among the cases did not change the results. Survival of the cases was shorter in the group with the concentration of POPs>median among cases, significantly so for the sum of PCBs (147 vs. 294 days), p,p'-DDE (134 vs. 302 days), and sum of chlordanes (142 vs. 294 days) in the high and low group, respectively. The results were based on a low number of cases and should be interpreted with caution.     

Sample Matrix Interference in Immunoassays for Organochlorine Residues in Plant-derived Foods and Some Strategies for Their Removal

Immunoassays for two groups of organochlorine insecticides, cyclodienes (endosulfan and heptachlor) and DDT were applied to the analysis of a diverse range of plant-derived foods. Water-miscible solvent extracts of high-moisture, low-fat foods such as cauliflower, cabbage, green and red blue grapes and tomato caused little or no interference with the assays, enabling methanol or acetonitrile extracts of the foods to be analysed directly by immunoassay, after dilution in assay buffer. Reasonable recoveries of spikes of these pesticides were obtained by direct analysis of extracts of spiked commodities, with reliable detection down to 0.025 mg kg^-1 heptachlor or endosulfan and 0.1 mg kg^-1 DDT in the commodities. Acetonitrile extracts of milk could also be analysed directly for DDT. In contrast, extracts of low moisture, non-fatty (rice) and fatty (cottonseed) food commodities interfered appreciably with the assays, reducing assay colour and detection sensitivity. Some simple cleanup methods were developed to remove interference and enable detection of spiked organochlorines in these foods. Extracts of coloured foods, such as tea, coffee and spinach caused similarly major interference in the assays, and a number of simple clean-up methods were ineffective in removing interference. However, use of an immunoaffinity chromatography method for cyclodienes enabled quantitative recoveries to be obtained in extracts of several of these foods when analysed by either ELISA or gas chromatography. Direct analysis was suited for screening purposes but immunoaffinity chromatography results were more quantitative. These results indicate that ELISAs can be applied under developing country conditions to a range of diverse foods, but that cleanup strategies need to be tailored to different types of foods.     

Distribution of organochlorines and PCB congeners in Korean human tissues

In order to investigate the residual amounts of organochlorines and polychlorinated biphenyls (PCBs) in Korean human tissues (blood, adipose tissue, liver, kidney cortex, and lung), the samples were collected from the autopsied cadavers of 40 men and 40 women (from teens to seventies of age). Alpha-BHC, beta-BHC, gamma-BHC, delta-BHC, p,p'-DDT, p,p'-DDD, p,p'-DDE, endrin, dieldein, aldrin, and 7 marker PCBs (28, 52, 101, 118, 138, 153, and 180) were determined in human tissues. The levels of organochlorines and PCB congeners indicated that they have been widely distributed in Korean human body. Positive correlations in terms of age were observed for the following cases: p,p'-DDE, p,p'-DDT, Sigma-DDT, PCB 118, PCB 138, PCB 153, and Sigma-PCB in the adipose tissue, and p,p'-DDE in the lung. Concentration of these compounds showed a significant age-related increase. Accumulation of these compounds in aged people revealed that these compounds were more slowly eliminated in our environment and risk assessment was necessary for further proper action. Significant differences in the levels of PCBs between genders were found for PCB 118 in the adipose tissue and PCB 138 in the liver. Positive correlation coefficients between tissues were detected with p,p'-DDE and p-BHC.     

Using Blood Plasma for Monitoring Organochlorine Contaminants in Juvenile White Sturgeon, <Emphasis Type="Italic">Acipenser transmontanus</Emphasis>, from the Lower Columbia River

Organochlorine (OC) pesticide concentrations in blood plasma samples from 88 juvenile white sturgeon collected from the lower Columbia River were measured and compared to plasma sex steroid and OC tissue levels previously measured in corresponding fish. Significant squared correlation coefficients between ∑ DDT concentrations in sturgeon plasma and gonads and livers were 0.37 and 0.32, respectively. Significant negative correlations between plasma testosterone concentration and plasma ∑ DDT concentration in male fish (r² = 0.26), plasma 17β estradiol concentration and plasma ∑ DDT concentration in female fish (r² = 0.38) and condition factor and plasma ∑ DDT concentration in all fish were found (r² = 0.17). These results suggest that blood plasma may be a suitable nondestructive method for monitoring adult sturgeon population for persistent OC contaminants.     

Chronic dietary exposure to environmental organochlorine contaminants induces thyroid gland lesions in Arctic foxes (Vulpes lagopus)

The impact of dietary organochlorine (OC) exposure on thyroid gland pathology was studied in farmed male Arctic foxes (Vulpes lagopus). The exposed group (n=16) was fed a diet based on wild minke whale (Balaenoptera acutorostrata) blubber as a main fat source in order to mimic the exposure to OC cocktails in the Artic environment. This resulted in an exposure of approximately 17 μg ∑OC/kg day and a ∑OC residue adipose tissue and liver concentration of 1700 and 4470 ng/g l.w., respectively, after 16 months of exposure. Control foxes (n=13) were fed a diet with pork (Sus scrofa) fat as a main fat source containing significantly lower OC concentrations. The food composition fed to the control and exposed group was standardized for nutrient contents. Four OC-related histopathological changes were found: (1) flat-epithelial-cell true thyroid cysts (TC) characterized by neutral content; (2) remnants of simple squamous epithelial-cell embryonic ducts containing neutral debris (EDN); (3) remnants of stratified squamous epithelial-cell embryonic ducts containing acid mucins often accompanied with debris of leukocyte inflammatory nature (EDM) and (4) disseminated thyroid C-cell hyperplasia (HPC). Of these, the prevalence of TC, EDN and HPC was significantly highest in the exposed group (χ² test: all p<0.04). The study shows that the OC mixture in minke whale blubber may cause development of thyroid gland cysts, C-cell hyperplasia and increase the prevalence of cystic remnants of embryonic ducts. The mechanism causing these effects could include endocrine disruption of the hypothalamus-pituitary-thyroid (HPT) axis, a disturbance of the calcium homeostasis/metabolism or energy metabolism or immune suppression. Because concentrations of OCs are higher in wild Arctic foxes, it is likely that these animals could suffer from similar OC-induced thyroid gland pathological and functional changes.     

Target-specific action of organochlorine compounds in reproductive and nonreproductive tissues of estrogen-reporter male mice

Organochlorines are lipophylic molecules that accumulate in the fat where they remain for years. During weight loss, they are mobilized and their concentration increases in blood. The present work tests, in transgenic estrogen-reporter mice (ERE-tK-LUC), whether this increase is sufficient to modulate the estrogen receptors (ERs) in the whole body. Three weak estrogens were studied: p,p'DDT [1,1,1-trichloro2,2-bis(p-chlorophenyl) ethane], p,p'DDE [1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene], and betaBHC [beta-benzene-hexachloride]. Dose-dependent analysis of reporter expression (luciferase) were performed in tissues of acutely treated mice. A body map of ER activation was obtained. All these chemicals modulated the reporter, although with a different efficiency and depending upon the tissue analyzed. Induction was confirmed in the liver by determining the expression of the endogenous progesterone receptor (PR) gene, at the dose and time point at which the luciferase gene was maximally induced. After experimental accumulation in the fat tissue, followed by a 48-h period of fasting, we tested whether these compounds could be mobilized to reach sufficient levels to activate the ERs in selected reproductive and nonreproductive tissues (testicle, prostate, liver, and lung). This experimental setting produced results that were different than those obtained following acute treatments. In loaded mice, fasting induced betaBHC mobilization resulted in strong ER activation in the liver and the lung, which was blocked by ICI-182780. p,p'DDT mobilization had no effect in these tissues, but it acted efficiently in the prostate and testis. betaBHC inhibited the ERE-mediated reporter in the testicle and induced the reporter in the prostate. In this tissue, betaBHC action was not inhibited by the anti-estrogen ICI-182780. During fasting, betaBHC, p,p'DDT, and metabolite p,p'DDE increased in blood concentration, from 2.25 +/- 0.25, 0.51 +/- 0.09, and 0.38 +/- 0.06 microg/ml to 8.24 +/- 0.95, 4.52 +/- 0.68, and 5.06 +/- 0.57 microg/ml, respectively. The effect produced by these organochlorines in the liver correlates with the modulation of the ERalpha protein. We conclude that these organochlorines modulate differently the expression of estrogen-regulated genes in male mice. Their effect is tissue- and compound-specific and is dependent on the energetic balance.     

Association between serum levels of organochlorine pesticides and sex hormones in adults living in a heavily contaminated area in Brazil

BackgroundSeveral studies have investigated the effects of organochlorine (OC) pesticides on adverse reproductive outcomes. However, few previous studies explored their effects on sex hormones.ObjectiveTo examine the association between serum concentrations of OC pesticides and levels of sex hormones in adult population in a rural area in Brazil heavily contaminated with these pesticides.MethodsA cross-sectional study with 304 men and 300 women was undertaken. Wet weight serum concentrations of 19 OC pesticides (dichloro-diphenyl-trichloroethane [DDT] and hexachlorocyclohexane [HCH], among others) were determined in all participants. Testosterone levels were obtained for men and estradiol, progesterone, prolactin, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) for women. Associations between OC pesticides and sex hormones were evaluated using linear regression models.ResultsPrevalence of women with non-physiological hyperprolactinemia was 4%. After adjusting for serum lipids and confounders, heptachlor and o,p′-DDT concentrations in men were associated with lower testosterone levels, while peri- and postmenopausal women (N = 77) showed inverse associations between LH and hexachlorobenzene (HCB), p,p′-DDT, p,p′-DDD (dichloro-diphenyl-dichloroethane), endosulfan 1 and 2, aldrin and mirex, as well as between FSH and p,p′-DDD, endosulfan 1 and aldrin. Premenopausal women (N = 210) did not show statistically significant associations between OC pesticides and sex hormones.ConclusionsInverse associations between OC pesticide concentrations and testosterone in men and LH and FSH in peri-/postmenopausal women, together with the high proportion of women with elevated prolactin, suggest that these OC compounds may have triggered anti-androgenic effects in men and estrogenic effects in women in this population.     

Environmental toxicant-induced maladaptive mitochondrial changes: A potential unifying mechanism in fatty liver disease?

Occupational and environmental exposures to industrial chemicals are well known to cause hepatotoxicity and liver injury. However, despite extensive evidence showing that exposure can lead to disease, current research approaches and regulatory policies fail to address the possibility that subtle changes caused by low level exposure to chemicals may also enhance preexisting conditions. In recent years, the conceptual understanding of the contribution of environmental chemicals to liver disease has progressed significantly. Mitochondria are often target of toxicity of environmental toxicants resulting in multisystem disorders involving different cells, tissues, and organs. Here, we review persistent maladaptive changes to mitochondria in response to environmental toxicant exposure as a mechanism of hepatotoxicity. With better understanding of the mechanism(s) and risk factors that mediate the initiation and progression of toxicant-induced liver disease, rational targeted therapy can be developed to better predict risk, as well as to treat or prevent this disease.