SEARCH · PubMed Health

Results for “environmental persistence”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 145 records · Page 8Linked to original sources

PubMed2002

Stimulation of calbindin-D(9k) mRNA expression in the rat uterus by octyl-phenol, nonylphenol and bisphenol.

Quantification of estrogen-induced changes in the expression levels of endogenous genes such as pS2 and vitellogenin could be an assay to detect estrogenicity of chemicals. Considering its regulation by estrogen, in the present study, we hypothesize that the calbindin-D(9k) (CaBP-9k) gene has the possibility as a biomarker for estrogenic response of the environmental estrogens. We analyzed the time- and dose-dependent CaBP-9k mRNA expression in the immature rats by 3-day injection of 17beta-estradiol (E2) and alkylphenol acid [octyl-phenol (OP) and nonylphenol (NP)] and bisphenol A(BPA)) which are environmentally persistent and reported to have some estrogenic activity in experimental test systems. The expression of CaBP-9k mRNA was compared with uterotropic response of the compounds. A significant increase in CaBP-9k mRNA expression was observed when treated with 1000 mg/kg body weight (BW) per day of OP (18-fold versus control), NP (17-fold versus control) and BPA (6-fold versus control) for 3 days in dot blot assays. Using Northern blot analysis, a more dramatic increase of CaBP-9k mRNA expression was observed when treated with 1000 mg/kg BW per day of OP (132-fold versus control) and NP (113-fold versus control) for 3 days. Treatment with 10 and 100 mg/kg BW per day of NP and 100 mg/kg BW per day of OP for 3 days induced a small but significant increase in CaBP-9k mRNA expression. As expected, a single dose of E2 (40 microg/kg BW per day) for 3 days induced a significant increase in CaBP-9k mRNA expression as revealed by dot (15-fold versus control) or Northern blot assay (102-fold versus control). In a time response experiment using Northern blot assay, a significant increase in CaBP-9k mRNA expression was observed as early as 3 h, peaked at 6 h and continued until 72 h after treatment with 1000 mg/kg BW per day of OP, NP, and 48 h after treatment with 1000 mg/kg BW per day of BPA. A similar time-dependent response was observed when assessed by dot blot assay. Uterotropic response of the compounds was determined and compared with CaBP-9k mRNA expression. The alkylphenolic compounds induced a significant increase in the uterine wet weight at 1000 mg/kg BW per day of OP and NP, not BPA. A strong correlation between in vivo uterotropic assay and CaBP-9k mRNA expression assay was observed. In order to investigate the possible mechanisms by which the compounds regulate CaBP-9k mRNA expression, we studied the effect of the compound on the ERalpha mRNA level using total RNA from the treated rats. The alkylphenolic compounds as well as E2 stimulate the expression of ERalpha mRNA in a similar pattern to that of CaBP-9k mRNA in terms of dose- and time-dependent response. Strong regulation of CaBP-9k mRNA expression by E2 and the environmental estrogens and its correlation with in vivo uterotropic assay suggest that CaBP-9k gene can be used as a biomarker gene for assaying estrogenicity of putative estrogenic compounds.

Animals↗

PubMed2001

Effect of highly bioaccumulated polychlorinated biphenyl congeners on estrogen and androgen receptor activity.

Polychlorinated biphenyls (PCBs) are ubiquitous environmental persistent contaminants giving rise to potential health hazard. Some PCBs exert dioxin-like activities mediated through the aryl hydrocarbon receptor. Although reports on interaction with other nuclear receptors are sparce, some congeners are hypothesized to possess endocrine disruptive potential. Here we present evidence that the three PCBs most abundant in biological extracts, 2,2',3'4,4',5-hexachlorobiphenyl (PCB#138), 2,2',4,4',5,5'-hexachlorobiphenyl (PCB#153), and 2,2',3,4,4',5,5'-heptachlorobiphenyl (PCB#180) have pleiotropic effects on the estrogen- and androgen-receptor. In MCF-7 cells a slightly increased cell proliferation was observed at low concentrations (1-10 nM) in cells co-treated with 0.01 nM 17beta-Estradiol, whereas the compounds inhibited cell growth significantly at 1 and 10 microM. In reporter gene (ERE-tk-CAT) analysis the three congeners exhibited a significantly estrogen receptor-ligand mediated decrease of the chloramphenicol transferase activity in both control and 10 nM 17beta-estradiol induced MCF-7 cells. In addition, PCB#138 elicited a dose-dependent antagonistic effect on androgen receptor activity in transiently co-transfected Chinese Hamster Ovary cells with an IC(50), of 6.2 microM. In summary, this study indicate that the di-ortho, multiple-chloro substituted biphenyls, PCB#138, PCB#153 and PCB#180, can compete with the binding of the natural ligand to two nuclear receptors and thus possess the ability to interfere with sexual hormone regulated processes.

Androgen Receptor Antagonists↗

PubMed2001

Incorporation of endocrine disruption into chemical hazard scoring for pollution prevention and current list of endocrine disrupting chemicals.

Research continues to support the theory of endocrine disruption. Endocrine disruption is defined as the ability of a chemical contaminating the workplace or the environment to interfere with homeostasis, development, reproduction, and/or behavior in a living organism or it's offspring. Certain classes of environmentally persistent chemicals such as polychlorinated biphenyls (PCBs), dioxins, furans, and some pesticides can adversely effect the endocrine systems of aquatic life and terrestrial wildlife. The University of Tennessee, Knoxville (UTN), developed a method for hazard scoring chemicals for the aquatic ecosystem. The Indiana Clean Manufacturing Technology and Safe Materials Institute at Purdue University (CMTI) later expanded the scoring system to include terms for worker hazard as well as terms for contamination of soil and air quality, and for stratospheric ozone depletion. We call the CMTI chemical hazard score the Purdue score. At West Virginia University, two improvements of the Purdue chemical hazard score are developed, a normalizing of the term for soil contamination, and addition of hazard score terms for ecosystem endocrine disruption. The results of incorporating endocrine disruption terms into the hazard scoring equations resulted in increased hazard rankings, often substantially increased, for 26 endocrine disrupting chemicals (EDCs) among 200 Superfund chemicals. Because data suggesting human endocrine disruption from such chemicals is still controversial, no endocrine disruptor term has been added to the human toxicity portions of the chemical hazard scoring system at this time. The third product of this work is assembly of a current consolidated list of (1) established or probable, mostly synthetic, industrial chemical and medication EDCs and (2) suspect (less certain) synthetic and natural (phytoestrogen) possible endocrine disrupting chemicals, with the goal of contributing to future development of quantitative structure activity relationship software for predicting whether an untested chemical is likely to be an endocrine disruptor. We conclude that enough endocrine disrupting chemicals are now identified to make an attempt at developing structure activity estimates of disrupting potential worthwhile. Further, we conclude that within a group of 200 chemicals of concern to the US EPA, the addition of endocrine disrupting terms to the Purdue score substantially increases its representativeness in reflecting ecological exposure hazard. We have developed this enhanced Purdue score risk management tool to be of assistance to industry.

Animals↗

PubMedDate not supplied

Lipophil-mediated reduction of toxicants in humans: an evaluation of an ayurvedic detoxification procedure.

CONTEXT: Lipophilic toxicants have been associated with hormone disruption, immune system suppression, reproductive disorders, several types of cancer, and other diseases. Due to environmental persistence and bioaccumulation, body burdens of certain toxicants, such as dichlorodiphenyldichloroethylene (DDE) and polychlorinated biphenyls (PCBs), appear to be a health risk despite the toxicants' having been banned for decades. OBJECTIVE: To determine whether a safe, standardized, Ayurvedic detoxification procedure can mobilize lipid-soluble toxicants and stimulate their excretion. DESIGN: Cross-sectional and longitudinal evaluations. SETTING: Southeastern Iowa. PARTICIPANTS: In the cross-sectional study, 48 participants who had undertaken lipophil-mediated detoxification were compared with 40 control subjects. In the prospective, longitudinal evaluation, serum levels were measured in 15 subjects before and after they underwent the detoxification procedure. These 15 subjects served as their own controls. INTERVENTION(S): Ayurvedic lipophil-mediated detoxification procedure. MAIN OUTCOME MEASURE: Gas chromatographic analysis of 17 serum toxicant levels (9 PCB congeners and 8 pesticides or metabolites) on a lipid-adjusted and wet-weight basis (ng/g) as parts per billion. RESULTS: In the cross-sectional study, gas chromatographic analysis of 9 PCB congeners and 8 pesticides revealed that serum PCB levels were significantly lower in the detoxification subjects than in controls. Trans-nonachlor (TNC), p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE), oxychlordane, and hexachlorobenzene (HCB) levels were also markedly lower in the detoxification group. All subjects had undetectable levels of p,p'-DDT, lindane, and a-hexachlorocyclohexane (a-HCH). Beta-hexachlorocyclohexane (beta-HCH) levels were significantly higher in detoxification subjects than in controls. In the longitudinal evaluation, after treatment, mean levels of PCBs (46%) and beta-HCH (58%) declined significantly in the subjects. CONCLUSIONS: The higher beta-HCH levels in the subjects in the longitudinal study appear to be an anomaly related to diet. The results of the 2 studies generally suggest that lipophil-mediated detoxification may be effective in reducing body burdens of fat-soluble toxicants. As numerous people worldwide are at risk from high body burdens of such lipid-soluble agents, further studies to evaluate this procedure appear warranted.

Case-Control Studies↗

PubMed2000

Effects of polychlorinated biphenyls on the nervous system.

The neurological effects of polychlorinated biphenyls (PCBs) have been extensively investigated in humans and in animals. The main focus in human studies has been on the effects in neonates and young children, although studies of adults have also been conducted. A great deal of concern exists that even low levels of PCBs transferred to the fetus across the placenta may induce long-lasting neurological damage. Because PCBs are lipophilic substances, there is also concem that significant amounts might be transferred to nursing infants via breast milk. Studies in humans who consumed large amounts of Great Lakes fish contaminated with environmentally persistent chemicals, including PCBs. have provided evidence that PCBs are important contributors to subtle neurobehavioral alterations observed in newborn children and that some of these alterations persist during childhood. Some consistent observations at birth have been motor immaturity and hyporeflexia and lower psychomotor scores between 6 months and 2 years old. There is preliminary evidence that highly chlorinated PCB congeners, which accumulate in certain fish, are associated with neurobehavioral alterations seen in some newbom children. Subtle neurobehavioral alterations have also been observed in children bom to mothers in the general population with the highest PCB body burdens. Because of the limitations of epidemiological studies, these effects cannot be attributed entirely to PCB exposure. In one general population study, there was strong evidence that dioxins, as well as PCBs, were contributors to the neurobehavioral effects seen in exposed children. Children born to women who accidentally consumed rice oil contaminated with relatively high amounts of PCBs and chlorinated dibenzofurans (CDFs) during pregnancy also had neurodevelopmental changes. Studies in animals support the human data. Neurobehavioral alterations have been also observed in rats and monkeys following prenatal and/or postnatal exposure to commercial Aroclor mixtures, defined experimental congener mixtures, single PCB congeners, and Great Lakes contaminated fish. In addition, monkeys exposed postnatally to PCB mixtures of congeneric composition and concentration similar to that found in human breast milk showed learning deficits long after exposure had ceased. A few other generalizations can be made from the data in animals. It appears that ortho-substituted PCB congeners are more active than coplanar PCBs in modifying cognitive processes. In addition, one effect observed in both rats and monkeys--deficits on delayed spatial alternation--has been known to be induced by exposure to ortho-substituted PCBs, defined experimental mixtures, and commercial Aroclors. Both dioxin-like and non-dioxin-like PCB congeners have been shown to induce neurobehavioral alterations in animals. Changes in levels of neurotransmitters in various brain areas have also been observed in monkeys, rats, and mice. Of all the observed changes, the most consistent has been a decrease in dopamine content in basal ganglia and prefrontal cortex, but further research is needed before specific neurobehavioral deficits can be correlated with PCB-induced changes in specific neurotransmitters in specific brain areas.

Administration, Oral↗

PubMedDate not supplied

Comparative evaluation of hepatotoxic and nephrotoxic effects of aroclors 1221 and 1254 in female rats.

Polychlorinated biphenyls (PCBs) are persistent environmental pollutants. This study compared effects of two PCB mixtures, Aroclors 1221 (A1221) and 1254 (A1254) on serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), urea, creatinine and uric acid in female rats. Histopathological changes in the liver and kidney were also examined. A group of adult Wistar rats served as controls. Groups II and III were subcutaneously injected with A1221 and A1254 at 10 mg/kg every other day for 6 weeks. At the end of this period, all animals were decapitated and blood samples were collected. Serum urea, creatinine, uric acid, ALT, AST and ALP levels were determined. Liver and kidney were collected for histopathological examination. They were fixed in formaldehyde and processed for light microscopy. Both A1221 and 1254 significantly elevated serum ALT (p < 0.05) and AST (p < 0.01) levels compared to the control group. Serum ALP values were significantly increased by A1221 (p < 0.05), but they were unaffected in the A1254 group. Treatment with both A1221 and A1254 significantly increased serum levels of urea (p < 0.05), creatinine (p < 0.01) and uric acid (except in the A1221 group; p < 0.005). Distinct histopathological changes including renal corpuscular atrophy, peritubular vascular congestion and dilated cortical tubules, sinusoidal dilatation, congestion and mononuclear cell infiltration were observed. These findings suggest that PCBs may cause nephrotoxicity and hepatotoxicity in female rats.

Alanine Transaminase↗

PubMed2002

Aroclor 1254 alters morphology, survival, and gene expression in Xenopus laevis tadpoles.

PCBs are persistent environmental contaminants that cause a variety of adverse health effects in wildlife and humans. This article describes the use of signature gene expression patterns that link increased PCB exposure with progressive, adverse biological effects. Developing Xenopus laevis tadpoles of two age classes were exposed to the PCB mixture Aroclor 1254 for 2 days. Real-time PCR was used to quantitate mRNA expression for 11 physiologically relevant, potential bioindicator genes. Younger tadpoles (5 days postfertilization) were resistant to Aroclor 1254 and showed few changes in gross morphology, swimming behavior, survival, or gene expression. Older tadpoles (11 days postfertilization) were more susceptible to Aroclor 1254. Exposure to 25 and 50 ppm Aroclor 1254 caused alterations in gross morphology and swimming behavior and statistically significant decreases in survival. These tadpoles showed statistically significant decreases in gene expression for 9 out of the 11 genes measured. Tadpoles exposed to 10 ppm showed incipient health changes but had gene expression profiles similar to the tadpoles treated with higher doses of Aroclor 1254. Tadpoles exposed to 1 ppm did not exhibit any observable adverse health effects, yet statistically significant decreases in gene expression occurred in these tadpoles (4 out of 11 genes). After prolonged exposure, tadpoles exposed to 1 and 10 ppm Aroclor 1254 exhibited health effects similar to those exposed to higher concentrations. Therefore, changes in expression of specific genes may serve not only as molecular bioindicators of Aroclor 1254 exposure but also as predictors of impending adverse health effects.

Animals↗

PubMed1992

Ovarian toxicity of hexachlorobenzene (HCB) in the superovulated female rat.

Hexachlorobenzene (HCB) is a persistent environmental contaminant which has been measured in human serum, fat, semen, and follicular fluid. In animal testing HCB has been shown to be a reproductive toxin. Discrepant results were obtained from prior studies concerning the effect of HCB treatment on ovarian steroidogenesis. The current study was designed to assess the impact of HCB on the ovary and gonadal steroid levels in the superovulated rat. Female Sprague-Dawley rats (n = 24) were dosed with HCB (0.0, 1.0, 10.0, or 100.0 mg/kg BW/day) for 21 days. All rats received 10 IU pregnant mare serum gonadotropin (PMSG) s.c. on day 18 of treatment and 15 IU of human chorionic gonadotropin (hCG) on day 20. A terminal blood sample was collected and circulating levels of estradiol (E2) and progesterone. (P4) were determined. Serum concentrations of P4 were significantly (p less than 0.0034) elevated by HCB treatment at all dose levels. Ovarian weights were significantly increased (p less than 0.05) in the lowest dose group only compared to the control group. Serum concentrations of E2, uterine weight, weight gain, and general animal health were not affected by HCB treatment. We conclude that during HCB treatment the rat ovary remains responsive to gonadotropin stimulation. Moreover, it is suggested that HCB effects on ovarian steroidogenesis are indirect.

Animals↗

PubMed2006

Involvement of the nitric oxide/protein kinase G pathway in polychlorinated biphenyl-induced cell death in SH-SY 5Y neuroblastoma cells.

Polychlorinated biphenyls (PCB) are persistent environmental contaminants whose chronic exposure can affect nervous system development and function. The cellular and molecular mechanisms underlying neuronal damage are not yet clear. In the present study, we investigated whether nitric oxide (NO) could be involved in aroclor 1254 (A1254; a PCB mixture)-induced cytotoxicity in SH-SY5Y human neuroblastoma cells. Prolonged exposure (24 hr) to A1254 (10-100 microg/ml) caused a dose-dependent reduction of cell viability that was attenuated in the presence of a calcium entry blocker, gadolinum (Gd(3+)) at 10 microM, a concentration able to block voltage-sensitive calcium channels. In addition, A1254 caused an increase of cytosolic calcium that was dependent on extracellular calcium, as measured by fura-2 videomicroscopy. A1254-induced calcium rise may stimulate NO production through an activation of neuronal NOS (nNOS). Indeed, the concomitant addition of the selective nNOS inhibitor N(omega)-propyl-L-arginine (NPLA) and A1254 prevented cell injury, suggesting that NO production plays a major role in A1254-evoked cell injury. Furthermore, the exposure (14 hr) to A1254 (30 microg/ml) produced an up-regulation of the expression of beta isoform of nNOS. This up-regulation was calcium dependent and was accompanied by an enhancement of NO production as demonstrated by an increase of nitrite formation. Moreover, A1254-induced cell injury was prevented when KT 5823, a selective cGMP/PKG inhibitor, was added concomitantly to 30 microg/ml A1254. These results suggest that PCB-induced cell death in neuroblastoma cells is mediated by an activation of the cGMP/PKG pathway triggered by NO production.

Calcium Channel Blockers↗

PubMed2006

Quantitative determination of perfluorinated surfactants in water by LC-ESI-MS/MS.

The surfactants perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS), and derivatives of the latter have emerged as globally distributed persistent environmental contaminants. Methods for their reliable quantitative determination at ppt-levels (ng/L) are needed in order to detect their main sources, to elucidate their environmental fate, and to identify potential sinks. The common method for water analysis involves preconcentration by SPE followed by LC coupled to ESI MS/MS (LC-ESI-MS/ MS). All sample preparation steps must be carefully optimized in order to arrive at reliable quantitative data. Two major aspects are important: (i) during SPE, contaminations may arise from materials containing traces of PFOA/S; (ii) during LC-ESI-MS/ MS, ionization yields are suppressed by matrix components and depend upon the analyte concentrations in the extracts. The levels of PFOA/S in the river Roter Main near Bayreuth have been determined using the optimized method.

Alkanesulfonic Acids↗

PubMed2006

Opposing action of curcumin and green tea polyphenol in human keratinocytes.

Persistent environmental insult can convert a normal cell into a cancer cell. However, various natural chemopreventive agents called antioxidants can retard this progression. We have recently explored the effects of several chemopreventive agents, including green tea polyphenol and curcumin, on normal human keratinocyte function. Our findings suggest that a bioactive polyphenol from green tea, (-)-epigallocatechin-3-gallate (EGCG), acts to increase involucrin gene expression, suggesting that EGCG treatment enhances normal human keratinocyte differentiation. Mechanistic studies indicate that EGCG alters mitogen-activated protein kinase cascade function to activate involucrin gene transcription via a Ras, MEKK1, MEK3, ERK1/2-p38delta cascade that targets AP1 and CAATT enhancer binding protein transcription factors. These findings suggest that EGCG may inhibit disease progression by promoting keratinocyte differentiation. Parallel studies indicate that not all antioxidants produce a similar response. Curcumin, an antioxidant derived from the turmeric, antagonizes the EGCG-dependent response by interfering in this signaling pathway. These studies suggest that different antioxidant may produce antagonistic effects in tissues.

Antioxidants↗

PubMed2001

Genotypic characterization of Pseudomonas aeruginosa strains recovered from patients with cystic fibrosis after initial and subsequent colonization.

Chronic infection by Pseudomonas aeruginosa (PA) in patients with cystic fibrosis (CF) is preceded by a period of colonization and acute infection. Early aggressive antibiotic treatment of initial colonisation may prevent or at least delay chronic pulmonary infection. We initiated treatment with a combination of IV beta-lactam tobramycin, followed by nebulized colistin when PA was first isolated from patients with CF. Subsequent serial PA isolates obtained from these colonized CF patients were characterized by means of molecular methods to determine whether they were genetically related to the initial strain. Initial colonization was eradicated in all 19 patients. All patients reacquired PA within 3-25 months during the 3 years of follow-up. Fourteen patients acquired a new PA strain with a distinct genotypic profile, suggesting a new source of contamination. Five patients had two PA isolates with identical genotypes, suggesting either previous undetected respiratory tract colonization or a persistent environmental source of contamination.

Administration, Inhalation↗

PubMed2005

Acaricide mode of action.

The last few years have seen the introduction of an unprecedented number of new classes of acaricides with novel or under-exploited modes of action, discovered by traditional screening. Acaricide research has uncovered several unrelated compounds that possess improved properties. Pyridaben, acequinocyl, diafenthiuron, etoxazole, spirodiclofen and bifenazate, in particular, are acaricides that are safe to beneficials, have low mammalian toxicity and short environmental persistence. Many of the new acaricides appear to affect mitochondrial respiration, and previously unknown targets affecting mite growth and development have been identified, offering new opportunities for mite control.

Animals↗

PubMed1994

The role of reactive oxygen species in the degradation of lindane and DDT.

We have studied the photodegradation reactions of lindane and DDT under sunlight (72 hr) or a solar simulator (2 hr) either directly or in presence of selected photodynamic sensitizers. Direct photolysis did not cause noticeable degradation of the pesticides (below 1% in both the cases). However, addition of benzophenone or rose bengal to the irradiation solution of lindane resulted in 88% and 47% degradation, respectively, under sunlight. Similar experiments carried out with DDT resulted in 89%, 50% and 32% degradation with benzophenone, rose bengal and methylene blue, respectively. All the photosensitizers used for the study have been shown to induce photooxidation reactions by generation of reactive oxygen species. These studies suggest that by employing certain naturally occurring photosensitizers with reactive oxygen generation potential under sunlight, an effective method for safe removal of pesticides and other environmentally persistent agents from the surface of earth can be developed.

Anthracenes↗

PubMed2001

Polychlorinated biphenyls, polychlorinated dibenzo-p-dioxins, and polychlorinated dibenzofurans as endocrine disrupters--what we have learned from Yusho disease.

Polychlorinated biphenyls (PCBs), polychlorinated dibenzo-p-dioxins, and polychlorinated dibenzofurans (PCDFs) are persistent environmental pollutants. In some areas wildlife reproduction has been affected by these compounds, which are recognized as endocrine disrupters. In 1968 in northern Kyushu in Japan about 2000 people were poisoned by PCBs and PCDFs (pyrolysis products of PCBs) which contaminated rice oil. Their condition was named "Yusho" disease. A similar poisoning by PCBs in Taiwan was named "Yu-Cheng" disease. The major symptoms of Yusho disease were dermal and ocular lesions, but some of the symptoms, such as irregular menstrual cycles and altered immune responses, were notable with respect to the endocrine disrupting activities of PCBs and related compounds. Several important observations relevant to the mechanisms of Yusho have been made from animal studies. For example, a coplanar PCB congener was shown to cause atrophy of the thymus and PCB administration was thought to alter androgen metabolism. The most tragic aspect of Yusho and Yu-Cheng diseases was the exposure of children to PCBs. In the case of Yu-Cheng, children exposed to PCBs in utero and lactationally were reported to have poor cognitive development. Intellectual impairment was also observed in children born to women who had eaten fish contaminated with PCBs in the United States. From animal studies, alterations in thyroid hormone status, modulation of protein kinase C, and changes in dopamine levels, etc. were proposed as the possible mechanisms for the adverse effects of PCBs on brain development. Whereas coplanar PCB and related congeners, e.g., 2,3,7,8-tetrachlorodibenzo-p-dioxin, induce gene expression via a ligand-dependent transactivating factor, the arylhydrocarbon receptor, alternative pathways for gene expression, e.g., c-Src and cross talk with the MAP kinase pathway, are also reviewed with respect to understanding the toxic mechanisms of these compounds. Finally, the "precautionary principle" is discussed for prevention of the health hazards caused by exposure to endocrine disrupters.

Animals↗

PubMed2000

Estrogen-induced vitellogenin mRNA and protein in sheepshead minnow (Cyprinodon variegatus).

Many environmentally persistent xenobiotic chemicals appear to disrupt normal endocrine function by acting as ligands for endogenous steroid receptors, including the estrogen receptor. Xenobiotics that bind to the estrogen receptor may elicit several effects, one of which is activating estrogen-responsive genes, such as vitellogenin (Vtg). Primers to vitellogenin mRNA have been used to amplify a portion of the coding sequence in sheepshead minnow (SHM) (Cyprinodon variegatus). Two Vtg cDNA fragments from SHM were isolated exhibiting 72% sequence homology and corresponding to the two Vtg genes identified in the mummichog, Fundulus heteroclitus. Using these Vtg cDNA fragments as sensitive genetic probes, we evaluated the initial estrogenic response of fish exposed to natural or anthropogenic chemicals. These probes were used to study in vivo gene induction in SHM exposed to 17beta-estradiol (E(2)) and ethinylestradiol (EE(2)) under controlled laboratory conditions. Hepatic Vtg mRNA was upregulated and plasma Vtg synthesis in estrogen-induced SHM was assessed. Two in vivo time-course experiments were conducted; a single injection of E(2) followed over 72 h and a double E(2) injection examined for 12 days. These two protocols provided evidence for differential hepatic Vtg mRNA regulation resulting from a single or a double injection. In a separate experiment using an aqueous flowthrough system, constant exposures to low doses of E(2) (200 ng/L) and EE(2) (100 ng/L) induced hepatic Vtg mRNA and plasma Vtg to levels comparable with the E(2) injections. Larger aqueous exposure doses (2000 ng/L E(2) or 1000 ng/L EE(2)) in the flowthrough experiment resulted in greater responses of hepatic Vtg mRNA and plasma Vtg at 7 days. Constant aqueous exposure to E(2) (2000 ng/L) or EE(2) (1000 ng/L) may thus be more effective than a single large-dose injection (5 mg/kg) to stimulate Vtg gene activation and synthesis.

Amino Acid Sequence↗

PubMed1999

Stimulation of oscillatory uterine contraction by the PCB mixture Aroclor 1242 may involve increased [Ca2+]i through voltage-operated calcium channels.

Polychlorinated biphenyls (PCBs) are persistent environmental pollutants associated with spontaneous abortion and shortened gestation length in women and animals. In previous studies, we showed that PCB mixtures and noncoplanar ortho-substituted PCB congeners increased contractions in pregnant rat uterus. In the present study, we hypothesized that the PCB mixture Aroclor 1242 (A1242) stimulates oscillatory uterine contraction in pregnant uterus by increasing intracellular calcium concentration ([Ca2+]i). Pretreatment of uterine strips with ryanodine or thapsigargin, to deplete specific intracellular calcium stores, did not prevent the increased frequency of oscillatory contraction due to 50 microM A1242, whereas thapsigargin effectively blocked carbachol-induced stimulation of uterine contraction. However, 100 microM A1242 was unable to increase contraction in the absence of extracellular calcium or in the presence of the voltage-operated L-type calcium channel blocker nifedipine. A1242 (100 microM) was observed to partially depolarize the cell membrane of myometrial cells from pregnant rats, as measured with a potential-sensitive carbocyanine dye. Changes of [Ca2+]i were monitored in single myometrial cells loaded with the fluorescent calcium-sensitive probe fura-2. Cells exposed to 100 microM A1242 showed a delayed and sustained increase of [Ca2+]i, and this increase was completely blocked in the absence of extracellular calcium or the presence of nifedipine. Therefore, the data suggest that depolarization of the cell membrane by A1242 enabled myometrial cells to increase [Ca2+]i through activation of voltage-operated calcium channels, and the increased [Ca2+]i consequently stimulated contraction of uterine smooth muscle.

Animals↗

PubMed2002

The polychlorinated biphenyl mixture aroclor 1254 induces death of rat cerebellar granule cells: the involvement of the N-methyl-D-aspartate receptor and reactive oxygen species.

Polychlorinated biphenyls (PCBs) are widespread persistent environmental contaminants that display a complex spectrum of toxicological properties, including neurotoxicity. The present study investigates the effects of the PCB mixtures Aroclor 1242 (A1242) and Aroclor 1254 (A1254), and the PCB congeners 126 (3,3',4,4',5,-PeCB) and 153 (2,2',4,4',5,5'-HxCB) on formation of reactive oxygen species (ROS) and cell death in cultured rat cerebellar granule cells. The increase of ROS and induction of cell death were assayed using the fluorescent probe 2,7-dichlorofluorescin diacetate (DCFH-DA) and the trypan blue exclusion assay, respectively. A1242 and A1254 and PCB 153 induced a concentration-dependent increase in cell death and ROS formation. A1254 was selected for mechanistic studies. When the cerebellar granule cells were exposed to 15 microM A1254 for 12 h, 95% of the cells died. Both PCB-mediated cell death and the increase of the ROS formation were inhibited by MK-801, demonstrating the importance of the N-methyl-D-aspartate receptor. Inhibitors of nitric oxide synthase and phospholipase A2 led to a significant reduction of the DCF fluorescence and cell death. The mitochondrial permeability transition pore blocker cyclosporin A and the antioxidant vitamin E also increased survival and reduced ROS formation. The results show a connection between cell death and free radical formation.

Animals↗