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Biomedical subjects

Paul D Jones

Publications and source records attributed to Paul D Jones.

At least 37 records · Page 2Linked to original sources
PubMed2005

Differential accumulation of polychlorinated biphenyl congeners in the aquatic food web at the Kalamazoo River Superfund site, Michigan.

A series of field studies were conducted to gain a better understanding of the bioaccumulation and dynamics of polychlorinated biphenyl (PCB) congeners in the aquatic food web of the Kalamazoo River flood plain. Representative species of passerine birds, mammals, fish, aquatic plants, invertebrates, and colocated sediments were collected from areas located within submerged portions of the former Trowbridge impoundment and also from areas located at an upstream reference location. In most matrixes, total concentrations of PCBs were significantly greater in the downstream study area compared to the upstream reference location. Patterns of PCB congeners varied among trophic levels due to selective bioaccumulation of more chlorinated congeners in upper trophic level organisms. There were no statistically significant differences in total PCB concentrations among sampling grids within either site or temporally among three sampling seasons between May and September. The greatest total PCB concentrations were detected in adult tree swallows (mean = 8.7 mg/kg wet weight (ww)) and fish (mean = 4.4 mg/ kg ww) collected from the former Trowbridge impoundment. Concentrations of total 2,3,7,8-tetrachlorodibenzo-p-dioxin equivalents (TEQs) were greatest in egg, nestling, and adult tree swallows collected from the former Trowbridge impoundment. There was not a significant correlation between concentrations of total PCBs and TEQs at either site in the mammalian or avian food webs. The relative potency of the mixture of PCBs, expressed as the ratio of TEQs to total PCBs, increased with trophic position in the avian and mammalian aquatic food webs located within the former Trowbridge impoundment.

Animals↗
PubMed2005

Differential accumulation of polychlorinated biphenyl congeners in the terrestrial food web of the Kalamazoo River Superfund site, Michigan.

A series of field studies was conducted to determine the bioaccumulation of polychlorinated biphenyl (PCB) congeners in the terrestrial food web of the Kalamazoo River flood plain. Samples included colocated soils, native plants likely to be consumed by wildlife, several taxa of terrestrial invertebrates, small mammals, passerine bird eggs, nestlings, and adults, and great horned owl plasma and eggs. Mean concentrations of total PCBs in samples from the former Trowbridge impoundment were 6.5 mg/kg dry weight for soils and 0.023, 0.13, 1.3, 1.3, 1.6, and 8.2 mg/kg wet weight for plants, small herbivorous mammals, depurated earthworms, shrews, great horned owl eggs, and house wren eggs, respectively. Historical data from the Kalamazoo River have reported Aroclor-equivalent total PCB concentrations in the terrestrial food web; however, the degree of environmental weathering of the parent PCB mixtures was unknown. In this study, earthworms and composite samples of coleoptera exhibited PCB congener patterns that were similar to patterns in colocated soils. However, in plants, less chlorinated PCBs (e.g., mono-, di-, tri-, and tetrachlorinated biphenyls) were predominant, and in small mammals, there was a notable enrichment of PCBs 153, 180, 138, 118, and 99. In general, concentrations of PCBs were lower in most biota than in soil from the Kalamazoo River Area of Concern (KRAOC) although there was a modest biomagnification of PCBs from lower trophic level biota to highertrophic levels. As a consequence of environmental weathering of PCBs in the terrestrial food web of the KRAOC, the relative potency of the PCBs (expressed as mg TEQs/kg PCBs) decreased from soil to most biota. While there was a general trend, as expected, in which concentrations of 2,3,7,8-tetrachlorodibenzo-p-dioxin equivalents (TEQs) increased with total PCBs, this relationship was rather poor (R2 = 0.13). Taken together, these data suggest that the differential accumulation of PCB congeners in the terrestrial food web can be explained by congener-specific differences in bioavailability from soil, exposure pathways, and metabolic potential of each of the food web components.

Animals↗
PubMed2005

Fluorescent substrates for soluble epoxide hydrolase and application to inhibition studies.

Inhibition of the mammalian soluble epoxide hydrolase (sEH) is a promising new therapy in the treatment of disorders resulting from hypertension and vascular inflammation. A spectrophotometric assay (4-nitrophenyl-trans-2,3-epoxy-3-phenylpropyl carbonate, NEPC) is currently used to screen libraries of chemicals; however this assay lacks the required sensitivity to differentiate the most potent inhibitors. A series of fluorescent alpha-cyanoester and alpha-cyanocarbonate epoxides that produce a strong fluorescent signal on epoxide hydrolysis by both human and murine sEH were designed as potential substrates for an in vitro inhibition assay. The murine enzyme showed a broad range of specificities, whereas the human enzyme showed the highest specificity for cyano(6-methoxy-naphthalen-2-yl)methyl trans-[(3-phenyloxiran-2-yl)methyl] carbonate. An in vitro inhibition assay was developed using this substrate and recombinant enzyme. The utility of the fluorescent assay was confirmed by determining the IC(50) values for a series of known inhibitors. The new IC(50) values were compared with those determined by spectrophotometric NEPC and radioactive tDPPO assays. The fluorescent assay ranked these inhibitors on the basis of IC(50) values, whereas the NEPC assay did not. The ranking of inhibitor potency generally agreed with that determined using the tDPPO assay. These results show that the fluorescence-based assay is a valuable tool in the development of sEH inhibitors by revealing structure-activity relationships that previously were seen only by using the costly and labor-intensive radioactive tDPPO assay.

Enzyme Inhibitors↗
PubMed2005

Effects of atrazine on CYP19 gene expression and aromatase activity in testes and on plasma sex steroid concentrations of male African clawed frogs (Xenopus laevis).

Some investigators have suggested that the triazine herbicide atrazine can cause demasculinization of male amphibians via upregulation of the enzyme aromatase. Male adult African clawed frogs (Xenopus laevis) were exposed to three nominal concentrations of atrazine (1, 25, or 250 microg atrazine/l) for 36 days, and testicular aromatase activity and CYP19 gene expression, as well as concentrations of the plasma sex steroids testosterone (T) and 17beta-estradiol (E2), and gonad size (GSI) were measured. There were no effects on any of the parameters measured, with the exception of plasma T concentrations. Plasma T concentrations in X. laevis exposed to the greatest concentration of atrazine were significantly less (p = 0.034) than those in untreated frogs. Both CYP19 gene expression and aromatase activities were low regardless of treatment, and neither parameter correlated with the other. We conclude that aromatase enzyme activity and gene expression were at basal levels in X. laevis from all treatments, and that the tested concentrations of atrazine did not interfere with steroidogenesis through an aromatase-mediated mechanism of action.

Animals↗
PubMed2005

Plasma concentrations of estradiol and testosterone, gonadal aromatase activity and ultrastructure of the testis in Xenopus laevis exposed to estradiol or atrazine.

The ultrastructure of testicular cells of adult male African clawed frogs (Xenopus laevis) exposed to either estradiol (0.1 microg/L) or 2-chloro-4-ethylamino-6-isopropyl-amino-s-triazine (atrazine; 10 or 100 microg/L) was examined by electron microscopy and compared to plasma concentrations of the steroid hormones, testosterone (T) and estradiol (E2), testicular aromatase activity and gonad growth expressed as the gonado-somatic index (GSI). Exposure to E2 caused significant changes both at the sub-cellular and biochemical levels. Exposure to E2 resulted in significantly fewer sperm cells, inhibition of meiotic division of germ cells, more lipid droplets that are storage compartments for the sex steroid hormone precursor cholesterol, and lesser plasma T concentrations. Although not statistically significant, frogs exposed to E2 had slightly smaller GSI values. These results may be indicative of an inhibition of gonad growth and disrupted germ cell development by E2. Concentrations of E2 in plasma were greater in frogs exposed to E2 in water. Exposure to neither concentration of atrazine caused effects on germ cell development, testicular aromatase activity or plasma hormone concentrations. These results suggest that atrazine does not affect testicular function. In contrast, exposure of male X. laevis to E2 led to sub-cellular events that are indicative of disruption of testicular development, and demasculinization processes (decrease of androgen hormone titers). These results indicate that atrazine does not cause responses that are similar to those caused by exposure to E2.

Analysis of Variance↗
PubMed2005

Quantitative RT-PCR methods for evaluating toxicant-induced effects on steroidogenesis using the H295R cell line.

Gene expression profiles show considerable promise for the evaluation of the toxic potential of environmental contaminants. For example, any alterations in the pathways of steroid synthesis or breakdown have the potential to Cause endocrine disruption. Therefore monitoring these pathways can provide information relative to a chemical's ability to impact endocrine function. One approach to monitoring these pathways has been to use a human adrenocortical carcinoma cell line (H295R) that expresses all the key enzymes necessary for steroidogenesis. In this study we have further developed these methods using accurate and specific quantification methods utilizing molecular beacon-based quantitative RT-PCR (Q-RT-PCR). The assay system was used to analyze the expression patterns of 11 steroidogenic genes in H295R cells. The expression of gene transcripts was measured using a real-time PCR system and quantified based on both a standard curve method using a dilution series of RNA standards and a comparative Ct method. To validate the optimized method, cells were exposed to specific and nonspecific model compounds (inducers and inhibitors of various steroidogenic enzymes) for gene expression profiling. Similar gene expression profiles were exhibited by cells treated with chemicals acting through common mechanisms of action. Overall, our findings demonstrated that the present assay can facilitate the development of compound-specific response profiles, and will provide a sensitive and integrative screen for the effects of chemicals on steroidogenesis.

Cell Line, Tumor↗
PubMed2005

Effects of atrazine on metamorphosis, growth, laryngeal and gonadal development, aromatase activity, and sex steroid concentrations in Xenopus laevis.

African clawed frogs (Xenopus laevis) were exposed to one of eight nominal waterborne concentrations including 0, 0.1, 1.0, 10, or 25 microg/L atrazine, 0.005% ethanol (EtOH), or 0.1mg/L estradiol (E2) or dihydrotestosterone (DHT) containing 0.005% EtOH. Frogs were exposed from 72 h posthatch until 2--3 months postmetamorphosis via a 3-day static renewal exposure regimen. Atrazine at concentrations between 0.1 and 25 microg/L did not significantly affect mortality, growth, gonad development, laryngeal muscle size, or aromatase activity in juvenile X. laevis. Male frogs exposed to 1.0 microg/L atrazine had lower E2 levels compared to controls, but this response was not consistent among other concentrations of atrazine. Male and female frogs exposed to DHT had larger laryngeal dilator muscle areas compared to controls. E2-exposed female frogs had decreased gonadal aromatase activity, and E2-exposed male frogs had statistically greater plasma concentrations of E2 compared to controls.

Animals↗
PubMed2005

Determination of fluoroquinolone antibiotics in wastewater effluents by liquid chromatography-mass spectrometry and fluorescence detection.

The occurrence of quinolone antibiotics (QAs) was investigated in wastewater effluents and surface river/lake waters in the US and Canada by using solid-phase extraction with mixed phase cation exchange disk cartridge and liquid chromatography-mass spectrometry (LC-MS) and liquid chromatography fluorescence detection (LC-FLD). Ofloxacin (OFL) was detected in secondary and final effluents of a wastewater treatment plant (WWTP) in East Lansing, Michigan, at concentrations of 204 and 100 ng/l, respectively. The mass flow calculation, estimated by multiplying the OFL concentration in the final effluent by the average influent volume of the WWTP, showed that the discharge of OFL to the river was 4.8 g/day. The OFL concentrations in wastewater effluents measured in this study are comparable to or less than those observed in several European countries. QAs were not detected in river and lake waters analyzed in this study, which may due to dilution effects and to the higher detection limits, relative to those reported previously. OFL concentrations were approximately 1-2 orders of magnitude lower than the EC50 concentrations for environmental bacterium. However, greater concentrations of other QAs in sewage sludge from WWTPs may result in cumulative effects. Considering that the sewage sludge is applied to the land as fertilizers, soil-dwelling organisms could experience greater exposures to such antibiotics. Monitoring studies of QAs in sewage from WWTPs and in sediment/soil near aquaculture facilities and livestock farms will be necessary for the evaluation of the environmental distribution and risk of these compounds.

Anti-Bacterial Agents↗
PubMed2005

Distribution of PCDDs and PCDFs in soils collected from the Denver Front Range--principal components analysis of diffuse dioxin sources.

BACKGROUND, AIMS AND SCOPE: The Rocky Mountain Arsenal (RMA) is a U.S. Army facility located northeast of Denver, Colorado that has been listed on the National Priorities List (NPL). It is currently being re-mediated under the authority of the Comprehensive Environmental Response, Compensation, and Liability Act of 1980 (CERCLA) and the Superfund Amendments and Reauthorization Act of 1986 (SARA). As part of the remediation activities at RMA, indications were found that a source of polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) had existed on the RMA. As a result, investigations were undertaken to assess the possible nature and extent of any potential sources of PCDDs and PCDFs on the RMA site. In addition, other studies were conducted that examined PCDD/PCDF contamination in the Denver area. The goal of these studies was to examine nature and extent of PCDD/PCDF contamination both on the RMA as well as in the surrounding Denver area. The intent of this study was to characterize sources of dioxins (PCDDs) and dibenzofurans (PCDFs) at low environmental concentrations which might have originated from diffuse sources in the Denver Colorado area and in particular, the Rocky Mountain Arsenal (RMA) using Principal Component Analysis (PCA). METHODS: Over 200 soil samples were collected from the RMA and the Denver area. From the RMA, soil was collected as part of three studies that included a (1) random site-wide sampling of the RMA, (2) soils from the Western Tier Parcel (WTP), and (3) soils from Historic Use areas. Denver area soil samples were collected from five different land use categories: Residential, Agricultural, Open Space, Commercial, and Industrial. PCA was conducted on concentrations of 17 2,3,7,8-substituted PCDD and PCDF congeners in 220 soil samples collected from the RMA and the Denver Front Range region. RESULTS AND DISCUSSION: PCA demonstrated the presence of possible minor sources of dioxins on the RMA. Current remediation efforts on RMA will result in the removal of these sources. Samples from the RMA were identified by the presence of a congener profile containing higher chlorinated PCDFs while the Denver Front Range areas were characterized by the presence of higher chlorinated PCDD congeners. The presence of a PCDF signature for the RMA samples does not necessarily indicate a major source of these contaminants on-site. Indeed, the relatively diffuse nature of the sample clusters would argue strongly against the presence of a single large source. Instead, the predominance of the PCDF congeners probably indicates the mixed industrial activities that took place on and near the site. CONCLUSION: PCA results indicate that PCDD/PCDF profiles in soils collected from the RMA differed from those collected from the outlying Denver areas but that a major source of these contaminants was not present. Rather, the diffuse nature of sample clusters from the PCA indicated that the congener profile of RMA samples was most likely a result of the mixed industrial activities that historically have taken place on and near the site. PCA also indicated that many of the 'open area' (peripheral site-wide) RMA soils samples did not differ from Denver are reference congener profiles. This finding was also true for samples collected from the WTP that were essentially indistinguishable from Off-RMA reference samples. In addition, total TEQ concentrations in soils collected from WTP were similar to those measured in soils collected from the Denver Front Range areas indicating that lack of a major source of PCDD/PCDF within the WTP zones of the RMA. RECOMMENDATION AND OUTLOOK: Analytical as well as statistical results of the soil congener data indicate that the WTP soils are indistinguishable from soils collected from non-industrial areas in the Denver area. This finding would support the recent 'de-listing' of the WTP from the other RMA areas and its transfer to other authorities in the Denver area.

Benzofurans↗
PubMed2004

Comparison of risk assessment methodologies for exposure of mink to PCBs on the Kalamazoo River, Michigan.

Risk assessments are generally based on exposures predicted by use of simple models of accumulation from abiotic compartments or the diet. The use of tissue-specific measurements of residue concentrations in wildlife tissues is more accurate and subject to less uncertainty, but these data are often not available. This report compares the results of two different site-specific approaches for assessing the risk of PCBs to mink residing along the Kalamazoo River, MI. The first approach was based on hepatic concentrations of PCBs and 2,3,7,8-tetrachlorodibenzo-p-dioxin equivalents (TEQs) of mink. The second approach was based on measured concentrations of both PCBs and TEQs in the diets of mink. For each of these methodologies, assessments were based on no observed adverse effect levels (NOAELs) or concentrations (NOAECs) and lowest observed adverse effect levels (LOAELs) or concentrations (LOAECs). Samples of mink (Mustela vison) and its diet were collected from within the Kalamazoo River Area of Concern (KRAOC) and an upstream reference area in the Fort Custer Recreation Area (FC). Hazard quotient (HQ) values were calculated based on congener-specific concentrations of PCBs or TEQs, several toxicity reference values (TRVs), and several assumed dietary compositions. Mean total hepatic concentrations of PCBs were 2.7 and 2.3 mg PCBs/kg, ww, in mink from the KRAOC and FC, respectively. HQs based on the LOAEC and mean hepatic PCB concentrations ranged from 0.37 to 0.87 at KRAOC and 0.31-0.73 at FC. HQs based on PCBs in the diet ranged from 0.20 to 1.8 at KRAOC and from 0.04 to 0.35 at FC. Dietary HQs were less than 10-fold different than tissue-based HQs.

Animals↗
PubMed2004

Assessment of the effects of chemicals on the expression of ten steroidogenic genes in the H295R cell line using real-time PCR.

The potential for a variety of environmental contaminants to disturb endocrine function in wildlife and humans has been of recent concern. While much effort is being focused on the assessment of effects mediated through steroid hormone receptor-based mechanisms, there are potentially several other mechanisms that could lead to endocrine disruption. Recent studies have demonstrated that a variety of xenobiotics can alter the gene expression or activity of enzymes involved in steroidogenesis. By altering the production or catalytic activity of steroidogenic or steroid-catabolizing enzymes, these chemicals have the potential to alter the steroid balance in organisms. To assess the potential of chemicals to alter steroidogenesis, an assay system was developed using a human adrenocortical carcinoma cell line, the H295R cell line, which retains the ability to synthesize most of the important steroidogenic enzymes. Methods were developed, optimized, and validated to measure the expression of 10 genes involved in steroidogenesis by the use of real-time quantitative reverse transcriptase PCR. The effects of several model chemicals known to alter steroid metabolism, both inducers and inhibitors, were assessed. Similar expression patterns were observed for chemicals acting through common mechanisms of action. Time-course studies demonstrated distinct time-dependent expression profiles for chemicals able to modulate steroid metabolism. The assay, which allows simultaneous analysis of the expression of numerous steroidogenic enzymes, would be useful as a sensitive and integrative screen for the many effects of chemicals on steroidogenesis.

Adrenal Cortex↗
PubMed2004

Identification, expression, and purification of a pyrethroid-hydrolyzing carboxylesterase from mouse liver microsomes.

Carboxylesterases are enzymes that catalyze the hydrolysis of a wide range of ester-containing endogenous and xenobiotic compounds. Although the use of pyrethroids is increasing, the specific enzymes involved in the hydrolysis of these insecticides have yet to be identified. A pyrethroid-hydrolyzing enzyme was partially purified from mouse liver microsomes using a fluorescent reporter similar in structure to cypermethrin (Shan, G., and Hammock, B. D. (2001) Anal. Biochem. 299, 54-62 and Wheelock, C. E., Wheelock, A. M., Zhang, R., Stok, J. E., Morisseau, C., Le Valley, S. E., Green, C. E., and Hammock, B. D. (2003) Anal. Biochem. 315, 208-222) and subsequently identified as a carboxylesterase (NCBI accession number BAC36707). The expressed sequence tag was then cloned, expressed in baculovirus, and purified to homogeneity. Kinetic constants for a large number of both type I and type II pyrethroid or pyrethroid-like substrates were determined. This esterase possesses similar kinetic constants for cypermethrin and its fluorescent-surrogate (k(cat) = 0.12 +/- 0.03 versus 0.11 +/- 0.01 s(-1)). Compared with their cis- counterparts, trans-permethrin and cypermethrin were hydrolyzed 22- and 4-fold faster, respectively. Of the four fenvalerate isomers the (2R)(alphaR)-isomer was hydrolyzed at least 1 order of magnitude faster than any other isomer. However, it is unlikely that this enzyme accounts for the total pyrethroid hydrolysis in the microsomes because both isoelectrofocusing and native PAGE indicate the presence of a second region of cypermethrin-metabolizing enzymes. A second carboxylesterase gene (NCBI accession number NM_133960), isolated during a cDNA mouse liver library screening, was also found to hydrolyze pyrethroids. Both these enzymes could be used as preliminary tools in establishing the relative toxicity of new pyrethroids.

Animals↗
PubMed2004

Environmental fate and bioavailability of Agent Orange and its associated dioxin during the Vietnam War.

BACKGROUND: In 1996, the Committee on the Assessment of Wartime Exposure to Herbicides in Vietnam of the National Academy of Sciences' Institute of Medicine (IOM) issued a report on an exposure model for use in epidemiological studies of Vietnam veterans. This exposure model would consider troop locations based on military records; aerial spray mission data; estimated ground spraying activity; estimated exposure opportunity factors; military indications for herbicide use; and considerations of the composition and environmental fate of herbicides, including changes in the TCDD content of the herbicides over time, the persistence of TCDD and herbicides in the environment, and the degree of likely penetration of the herbicides into the ground. When the final report of the IOM Committee was released in October 2003, several components of the exposure model envisioned by the Committee were not addressed. These components included the environmental fate of the herbicides, including changes in the TCDD content over time, the persistence of TCDD and herbicides in the environment, and the degree of likely penetration of herbicides into the ground. This paper is intended to help investigators understand better the fate and transport of herbicides and TCDD from spray missions, particularly in performing epidemiological studies. METHODS: This paper reviews the published scientific literature related to the environmental fate of Agent Orange and the contaminant, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), and discusses how this affected the potential exposure to TCDD of ground troops in Vietnam. Specifically, the mechanisms of dissipation and degradation as they relate to environmental distribution and bioavailability are addressed. RESULTS: The evaluation of the spray systems used to disseminate herbicides in Vietnam showed that they were capable of highly precise applications both in terms of concentrations sprayed and area treated. Research on tropical forest canopies with leaf area indices (a measure of foliage density) from 2 to 5 indicated that the amount of herbicide and associated TCDD reaching the forest floor would have been between 1 and 6% of the total aerial spray. Studies of the properties of plant surface waxes of the cuticle layer suggested that Agent Orange, including the TCDD, would have dried (i.e., be absorbed into the wax layer of the plant cuticle) upon spraying within minutes and could not be physically dislodged. Studies of Agent Orange and the associated TCDD on both leaf and soil surface have demonstrated that photolysis by sunlight would have rapidly decreased the concentration of TCDD, and this process continued in shade. Studies of 'dislodgeable foliar residues' (DFR, the fraction of a substance that is available for cutaneous uptake from the plant leaves) showed that only 8% of the DFR was present 1 hr after application. This dropped to 1% of the total 24 hrs after application. Studies with human volunteers confirmed that after 2 hrs of saturated contact with bare skin, only 0.15-0.46% of 2,4,5-T, one of the phenoxy acetic acid compounds that was an active ingredient of Agent Orange, entered the body and was eliminated in the urine. CONCLUSIONS: The prospect of exposure to TCDD from Agent Orange in ground troops in Vietnam seems unlikely in light of the environmental dissipation of TCDD, little bioavailability, and the properties of the herbicides and circumstances of application that occurred. Photochemical degradation of TCDD and limited bioavailability of any residual TCDD present in soil or on vegetation suggest that dioxin concentrations in ground troops who served in Vietnam would have been small and indistinguishable from background levels even if they had been in recently treated areas. Laboratory and field data reported in the literature provide compelling evidence on the fate and dislodgeability of herbicide and TCDD in the environment. This evidence of the environmental fate and poor bioavailability of TCDD from Agent Orange is consistent with the observation of little or no exposure in the veterans who served in Vietnam. Appreciable accumulation of TCDD in veterans would have required repeated long-term direct skin contact of the type experienced by United States (US) Air Force RANCH HAND and US Army Chemical Corps personnel who handled or otherwise had direct contact with liquid herbicide, not from incidental exposure under field conditions where Agent Orange had been sprayed.

2,4,5-Trichlorophenoxyacetic Acid↗
PubMed2004

Plasma sex steroid concentrations and gonadal aromatase activities in African clawed frogs (Xenopus laevis) from South Africa.

Adult African clawed frogs (Xenopus laevis) were collected from a corn-growing region (CGR) and a non-corn-growing region (NCGR) with different exposure profiles for atrazine and related triazines. Physical, chemical, and biological parameters from the catchment areas were also measured. Frogs were surveyed for possible effects of exposure to triazine herbicides on plasma testosterone (T) and estradiol (E2) titers, gonadal aromatase activity, and gonad growth (GSI). Concentrations of both T and E2 varied among locations and were correlated to some accessory factors, such as pH, several ions, and metals. Greatest median plasma T concentrations (males: 19 ng/ml; females: 16 ng/ml) occurred in frogs inhabiting NCGR as compared to those from the CGR (males: 4 ng/ml; females: 1 ng/ml). Median E2 concentrations were also greater in frogs collected from the NCGR (males: 3 ng/ml; females: 28 ng/ml) than those in frogs from the CGR (males: 2 ng/ml; females: 5 ng/ml). Because some exposure to agricultural chemicals at both regions occurred, as did simultaneous exposures to multiple chemicals, a regression analysis was employed. Negative correlations were observed between plasma T concentrations and concentrations of atrazine, deisopropylatrazine, deethylatrazine, and tertbuthylazine in females and between T and diaminochlorotriazine in males. Estradiol in females exhibited a significant negative correlation with atrazine and deethylatrazine. No correlations were observed between gonadal aromatase activity or GSI and any of the agricultural chemicals measured. Median aromatase activities in ovaries varied among sampling sites ranging from 7 to >3000 times greater than those in males when measurable. Testicular aromatase activity was below the detection limit of the assay in male frogs at most of the sites. Although exposure to agricultural inputs did not affect aromatase activities, effects of atrazine or coapplied pesticides on sex steroid homeostasis cannot be excluded at this point.

Agriculture↗
PubMed2003

Removal of estrogenic activity from municipal waste landfill leachate assessed with a bioassay based on reporter gene expression.

The leachate of a municipal waste landfill was tested for estrogenic activity using a reporter-gene-based bioassay with a human breast-cancer-derived cell line (MVLN cells). The leachate was processed with two different membrane-employing processes operating in parallel. One process consists of aerobic biological degradation, ultrafiltration, and subsequent adsorption to activated carbon. The second process was a reverse osmosis treatment of the raw leachate. Both processes are common in the treatment of landfill leachate. Here, the efficacy of the two processes to remove "estrogenicity" was compared. Both treatment processes removed more than 97% of the estrogenic activity, calculated as estradiol equivalents (EEQs), but they were not equally effective. After adsorption to activated carbon, no estrogenicity was detected, whereas concentrated effluent of the reverse osmosis treatment still elicited an estrogenic response in the bioassay. On the basis of chemical analysis, it is proposed that bisphenol A was responsible for the majority of estrogenic activity in the raw and treated leachate. Although the contribution of treated leachate to the estrogenic load on the aquatic environment seems to be low compared to that of sewage treatment works, the high estrogenic activity in raw landfill leachate stresses the necessity for the appropriate treatment of these leachates.

Benzhydryl Compounds↗
PubMed2003

Alterations in cell membrane properties caused by perfluorinated compounds.

The recent detection of perfluorinated compounds (PFCs) in wildlife from even remote locations has spurred interest in the environmental occurrence and effects of these chemicals. While the global distribution of PFCs is increasingly understood, there is still little information available on their effects on wildlife. The amphiphillic nature of PFCs suggests that their effects could be primarily on cell membranes. In this study we measured the effects of PFCs on membrane fluidity and mitochondrial membrane potential using flow cytometry and effects on membrane permeability using cell bioassay procedures (H4IIE, MCF-7, PLHC-1). Of the PFCs tested, only perfluorooctane sulfonic acid (PFOS) increased the permeability of cell membranes to the hydrophobic ligands used. Three PFCs were tested in the membrane fluidity assay: PFOS, perfluorohexane sulfonic acid (PFHS), and perfluorobutane sulfonic acid (PFBS). PFOS increased membrane fluidity in fish leukocytes in a dose-dependent fashion, while PFHS and PFBS had no effect in the concentration range tested. The lowest effective concentrations for the membrane fluidity effects of PFOS were 5-15 mg/l. Effects on mitochondrial membrane potential occurred in the same concentration range as effects on membrane fluidity. This suggests that PFOS effects membrane properties at concentrations below those associated with other adverse effects.

Alkanesulfonic Acids↗
PubMed2003

Examination of reproductive endpoints in goldfish (Carassius auratus) exposed in situ to municipal sewage treatment plant effluent discharges in Michigan, USA.

Effects of representative mid-Michigan (USA) wastewater treatment plant (WWTP) effluents on the reproductive physiology of common goldfish (Carassius auratus) were assessed in situ by measuring plasma concentrations of vitellogenin (VTG), 17 beta-estradiol (E2), and testosterone (T), and evaluating gonad histology. Caged adult male and female goldfish were exposed for six weeks to WWTP effluents. One riverine site and one lacustrine site were included as references for comparison to WWTP sites. There was differential growth and gonadal development among locations, which confounded the interpretation of biomarker responses. A linear contrast model was developed by analysis of covariance, and adjusted values were developed for concentrations of VTG, E2, and T in the plasma of both male and female fish. In general, VTG concentrations were significantly less in male than in female goldfish. Most concentrations of VTG in male goldfish were less than the method detection limit. There were no significant differences in plasma VTG of either male or female goldfish among locations or between sites at WWTPs and reference sites. Concentrations of E2 in the plasma of female goldfish were similar among WWTP sites, all of which were less than in females at a pond reference location. Concentrations of E2 in the plasma of male goldfish were similar at all WWTP locations, except for one, where they were greater. No consistent trends in hormone concentrations or gonadal histology could be attributed to putative endocrine disrupter exposure in WWTP effluents. The results indicate that the risk for estrogen agonist exposure below these mid-Michigan WWTPs is small.

Animals↗