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Journal ArticleDOI

Estrogenic Activities of 517 Chemicals by Yeast Two-Hybrid Assay

TL;DR: A simple and rapid screening method using the yeast two-hybrid system based on the ligand-dependent interaction of nuclear hormone receptors with coactivators to test the estrogenic activity of chemicals.
Abstract: One of the urgent tasks in understanding endocrine disruptors (EDs) is to compile a list of suspected substances among the huge number of chemicals by using the screening test method. We developed a simple and rapid screening method using the yeast two-hybrid system based on the ligand-dependent interaction of nuclear hormone receptors with coactivators. To date, we have tested the estrogenic activity of more than 500 chemicals including natural substances, medicines, pesticides, and industrial chemicals. 64 compounds were evaluated as positive, and most of these demonstrated a common structure; phenol with a hydrophobic moiety at the para-position without bulky groups at the ortho-position. These results are expected to facilitate further risk assessment of chemicals.

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Citations
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Journal ArticleDOI
TL;DR: Two reasons of the absence of adverse effects on semen quality might be suggested: lower paraben exposure level of the subjects and small sample size.
Abstract: Possible relationship between semen quality (semen volume, sperm concentration and sperm motility) and parabens exposure was investigated in male partners of couples who visited a gynecology clinic in Tokyo for infertility consultation (n = 42, 36.8 ± 5.4 years). Semen parameters were measured according to WHO guideline at the clinic, and urinary methyl- (MP), ethyl- (EP), propyl- (PP) and butyl (BP) paraben concentrations were measured with liquid chromatography-tandem mass spectrometry. Geometric mean urinary concentrations (geometric standard deviation) of the subjects were 48.2 (4.52), 1.88 (4.72), 1.13 (6.75) and 0.184 (11.1) ng/mL for MP, EP, PP and BP, respectively. No significant association was found between semen parameters and urinary paraben concentrations in multiple regression analyses and logistic regression analyses. Two reasons of the absence of adverse effects on semen quality might be suggested: lower paraben exposure level of the subjects and small sample size. Further investigation of effect of paraben exposure among general male population at environmental levels is warranted.

19 citations

Journal Article
TL;DR: There is not always possible to identify causal relationships between organochlorine exposure and deleterious health effects, andLimitations in the ability to identify or to quantify causal relationships are occasionally misinterpreted as evidence of safety.
Abstract: Organochlorines are a various group of synthetic chemicals that include polychlorinated biphenyls (PCBs), dibenzo- p- dioxiins and organochlorine pesticides. Human exposure to organochlorine substances may occur through inhalation of air, ingestion of food and water and skin absorption. Human exposure to organochlorines may occur not only during adulthood but also during prenatal and neonatal period. The developing fetus is exposed to organochlorines through placental transfer and the neonate through lactation. Organochlorine compounds exert many toxic effects on human health, such as, hormone related conditions (endometrisios, infertility), cancer of male and female reproductive system, developmental toxicity, neurotoxicity and immunotoxicity. The majority of these effects may be due to the ability of organochlorines to alter the levels of certain hormones, enzymes, growth factors and neurotransmitters and to induce key genes (cytochrome P-450 1A1 gene) involved in metabolism of steroids and xenobiotics. However, there is not always possible to identify causal relationships between organochlorine exposure and deleterious health effects. Limitations in the ability to identify or to quantify causal relationships are occasionally misinterpreted as evidence of safety. Frequently, governments have to wait until sufficient scientific information of harm is established before they act to prevent harm. However, failure to take precautionary action may have severe social, economic and health costs.

19 citations


Cites background from "Estrogenic Activities of 517 Chemic..."

  • ...Up till now, more than 500 chemicals have found to be weakly estrogenic, including many common chemicals, such as pesticides and plastics (40,41)....

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Journal ArticleDOI
TL;DR: A solid-phase extraction method compatible with the E1 + E2 + E3 immunoassay demonstrated that this combined approach of extraction and immunoASSay had good potential for determining estrogen concentrations in environmental samples such as surface water in urban and agricultural ecosystems.
Abstract: Estrogens are a family of feminizing hormones that are excreted by vertebrates. It has been documented that their presence in surface waters, even in the ng/L range, can have detrimental impacts on fish reproduction. Two competitive enzyme-linked immunosorbent assays using rabbit polyclonal antibodies were developed: one for 17beta-estradiol and a second one for 17beta-estradiol (E2)+estrone (E1)+estriol (E3). Two different conjugates were synthesized using the Mixed-anhydride (for the 17beta-estradiol ELISA) and the Mannich (for the E1 + E2 + E3 ELISA) reactions. The 17beta-estradiol ELISA was highly specific with an IC(50) of 243 ng/mL for 17beta-estradiol. The E1 + E2 + E3 ELISA exhibited cross-reactivity with estrone (85%) and estriol (62%) with an IC(50) of 18 ng/mL for 17beta-estradiol. Cross-reactivity was tested against 13 chemically related compounds and both immunoassays showed significant cross-reactivity with two estradiol conjugates: beta estradiol-17-valerate and beta estradiol-3-benzoate (from 57 to 84 %) for which, to our knowledge, there are currently no commercially available ELISA. Characteristics (sensitivity, inter and intra assay variation, and cross-reactivity) of the E1 + E2 + E3 ELISA were further compared to those from a commercial Estriol ELISA. The commercial ELISA was more specific, sensitive and its inter-assay variation was less (9.5% compared to 10% for the E1 + E2 + E3 ELISA) but the E1 + E2 + E3 ELISA had less intra-assay variation (4% compared to 5% for the commercial ELISA). Finally, a solid-phase extraction method compatible with the E1 + E2 + E3 immunoassay demonstrated that this combined approach of extraction and immunoassay had good potential for determining estrogen concentrations in environmental samples such as surface water in urban and agricultural ecosystems.

19 citations


Cites methods from "Estrogenic Activities of 517 Chemic..."

  • ...Crossreactivity was tested against 13 compounds including three other natural estrogenic compounds (estrone, estriol and 17α-estradiol), one gestagen (progesterone), one androgen (testosterone), two corticosteroids (aldosterone, hydrocortisone), two naturally conjugated estrogens ([estradiol17 (B-D glucuronide) sodium salt], and [estradiol-3 (B-D glucuronide) sodium salt]), three synthetic estrogens (ethynyl estradiol, β-estradiol-17-valerate and β estradiol3-benzoate) and one herbicide (atrazine) with known estrogenic activity.[21] For cross-reactivity determination, all chemicals were of analytical grade and purchased from Sigma-Aldrich Chemical Company (St....

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Journal ArticleDOI
TL;DR: Results indicate that PAHs taken into mother rat by the inhalation of DE are transferred into fetuses via placenta and into breast milk, the first report to clarify the transportation of inhaledPAHs into Fetuses and breast milk from mother rats.
Abstract: Polycyclic aromatic hydrocarbons (PAHs) were analyzed in maternal blood and fetuses from Fischer 344 rats exposed to diesel exhaust (DE) during pregnancy, and in breast milk from rats exposed to DE during pregnancy and lactation using high performance liquid chromatography with fluorescence detection. Concentrations of phenanthrene (Phe), anthracene (Ant) and benz[a]anthracene (BaA) were significantly higher in maternal blood of the DE group than those of the control group. Concentration of Phe in fetuses of the DE group was significantly higher than those of the control group. Concentrations of fluorene, Ant, fluoranthene (Flu), pyrene (Pyr), BaA and chrysene (Chr) tended to be higher in fetuses of the DE group. The levels of Ant, Flu, Pyr and Chr in breast milk from the DE group were significantly higher than those of the control group. These results indicate that PAHs taken into mother rat by the inhalation of DE are transferred into fetuses via placenta and into breast milk. This is the first report to clarify the transportation of inhaled PAHs into fetuses and breast milk from mother rats.

19 citations

Journal ArticleDOI
TL;DR: Hydrolysis of methiocarb and carbaryl and oxidation of metHIocarb to the sulfoxide markedly modified the estrogenic and antiandrogenic activities of meethiocar and carb Daryl.

18 citations

References
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Book
01 Jan 1996
TL;DR: The cause of disruptions in animal breeding cycles, accompanied by increases in birth defects, sexual abnormalities and reproductive failure, is traced to the pervasive presence in the environment of chemicals that mimic hormones and trick the reproductive system.
Abstract: For years, scientists have noticed disruptions in animal breeding cycles, accompanied by increases in birth defects, sexual abnormalities and reproductive failure. Humans are not immune either, with sperm counts dropping by as much as 50% in recent decades and with women seeing a rise in hormone-related cancers, endometriosis and other disorders. This book traces the cause of these aberrations and diseases to the pervasive presence in the environment of chemicals that mimic hormones and trick the reproductive system. The conclusions are as obvious as they are inescapable - unless we make vital changes in the way we manufacture and employ the artefacts of our "good life", there will be no life at all.

917 citations