The proestrogen methoxychlor is active in a yeast oestrogenicity assay in the absence of metabolism

Elsby, Robert; Maggs, James L.; Ashby, John; Park, B.K.

doi:10.1016/s0300-483x(00)90311-1

Cited by 5 publications

(6 citation statements)

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“…BPA increased cell numbers in a dose-dependent manner from 10 -7 to 10 -5 M. 3-OH-BPA at the concentration of 10 -7 −10 -6 M caused a slight increase in cell numbers, while the proliferation rate was lower than that of BPA. These results are the same as previous results ( , ). The proliferation potency of DHMS was the strongest of the metabolites of BPA; the compound increased significantly at the lowest concentration, 10 -9 M. BPA-COOH also increased slightly in cell numbers at 10 -5 and 10 -4 M. BPA-OH did not affect on MCF-7 cells proliferation.…”

Section: Resultssupporting

confidence: 92%

“…As for the BPA metabolites, BPA glucronide (which is found in rodent urine, liver microsomes, and hepatocytes) did not interact with the estrogen receptors and did not affect estrogen activity in MCF-7 cells (24,25). Estrogen activity of 2-(3,4-dihydroxyphenyl)-2-(4-hydroxyphenyl)propane (3-OH-BPA), a minor metabolite in liver microsomes of human and rats and rat hepatocytes was approximately 10 times less than that of BPA in MCF-7 cells (23) and in the coupled microsomal metabolism-yeast estrogenicity assay (26). On the other hand, there have been a few studies on the estrogenic activity of BPA metabolites produced by bacteria.…”

Section: Introductionmentioning

confidence: 99%

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Environmental Fate of Bisphenol A and Its Biological Metabolites in River Water and Their Xeno-estrogenic Activity

Suzuki

Nakagawa

Takano

et al. 2004

Environ. Sci. Technol.

215

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Monitoring of bisphenol A [BPA; 2,2-bis(4-hydroxyphenyl)propane] and its biological metabolites [4,4'-dihydroxy-alphamethylstilbene (DHMS), 2,2-bis(4-hydroxyphenyl)-1-propanol (BPA-OH), 2,2-bis(4-hydroxyphenyl)propanoic acid (BPA-COOH), and 2-(3,4-dihydroxyphenyl)-2-(4-hydroxyphenyl)propane (3-OH-BPA)] in river waters was performed by solid-phase extraction and GC/MS determination. The concentrations of BPA, BPA-COOH, BPA-OH, and 3-OH-BPA in the river water ranged from 2 to 230 (8.8 x 10(-12) to 1.0 x 10(-9) M), from 5 to 75 (1.9 x 10(-11) to 2.9 x 10(-10) M), from 3 to 16 (1.2 x 10(-11) to 6.6 x 10(-11) M), and from 3 to 11 (1.2 x 10(-11) to 4.5 x 10(-11) M) ng L(-1), respectively. DHMS, an intermediate in the main degradation pathway of BPA, was not detected in any water sample. Under the aerobic conditions in the river water, BPA disappeared within 8 d of incubation, but BPA-COOH, BPA-OH, and tetraol remained in the supernatant after 14 d of incubation. For the xeno-estrogenic activity of BPA and the metabolites, their ability to bind to recombinant human estrogen receptor alpha in competition with fluorescence-labeled 17beta-estradiol was measured. Fifty percent inhibitory concentrations (IC50) of BPA, DHMS, 3-OH-BPA, and BPA-OH were approximately 1 x 10(-5), 1 x 10(-6), 3 x 10(-5), and 1 x 10(-2) M, respectively. In human cultured MCF-7 breast cancer cells, BPA increased cell numbers in a dose-dependent manner at concentrations from 10(-7) to 10(-5) M. For the BPA metabolites, DOHMS, 3-OH-BPA, and BPA-COOH caused the cells proliferation at concentrations from 10(-9) to 10(-6), from 10(-7) to 10(-6), and from 10(-5) to 10(-4) M, respectively. BPA-OH did not cause MCF-7 cells proliferation. These results indicate that BPA is mainly metabolized through oxidative rearrangement by bacteria in the river water, and intermediate bisphenols via minor metabolic pathways exist in river water. The presence of the bisphenols having the xeno-estrogenic effect suggests the necessity of monitoring those in river water, in the effluent waters from sewage plants, or in landfill leachate.

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Section: Resultssupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Environmental Fate of Bisphenol A and Its Biological Metabolites in River Water and Their Xeno-estrogenic Activity

Suzuki

Nakagawa

Takano

et al. 2004

Environ. Sci. Technol.

215

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“…Determination of UGT Activity-UGT assays were carried out as described previously (31). Briefly, incubations contained 50 mM TrisHCl buffer (pH 7.4), 5 mM MgCl 2 , 0.3 mg/ml Brij 58, GstP1/P2 (ϩ/ϩ) or GstP1/P2…”

Section: Methodsmentioning

confidence: 99%

Increased Constitutive c-Jun N-terminal Kinase Signaling in Mice Lacking Glutathione S-Transferase Pi

Elsby

Kitteringham

Goldring

et al. 2003

Journal of Biological Chemistry

141

106

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Glutathione S-transferase Pi (GSTP) detoxifies electrophiles by catalyzing their conjugation with reduced glutathione. A second function of this protein in cell defense has recently been proposed that is related to its ability to interact with c-Jun N-terminal kinase (JNK). The present study aimed to determine whether this interaction results in increased constitutive JNK activity in the absence of GSTP in GstP1/P2 (؊/؊) mice and whether such a phenomenon leads to the up-regulation of genes that are relevant to cell defense. We found a significant increase in constitutive JNK activity in the liver and lung of GstP1/P2؊/؊ compared with GstP1/ P2 (؉/؉) mice. The greatest increase in constitutive JNK activity was observed in null liver and was accompanied by a significant increase in activator protein-1 DNA binding activity (8-fold) and in the mRNA levels for the antioxidant protein heme oxygenase-1 compared with wild type. Furthermore UDP-glucuronosyltransferase 1A6 mRNA levels were significantly higher in the livers of GstP1/P2 (؊/؊) compared with GstP1/P2 (؉/؉) mice, which correlated to a 2-fold increase in constitutive activity both in vitro and in vivo. There was no difference in the gene expression of other UDP-glucuronosyltransferase isoforms, manganese superoxide dismutase, microsomal epoxide hydrolase, or GSTA1 between GstP1/ P2 (؊/؊) and GstP1/P2 (؉/؉) mice. Additionally there was no phenotypic difference in the induction of heme oxygenase-1 mRNA after acetaminophen administration. This study not only demonstrates the role of GSTP as a direct inhibitor of JNK in vivo but also its role in regulating the constitutive expression of specific downstream molecular targets of the JNK signaling pathway.

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“…Investigations of BPA metabolism in vivo [36,37] and in vitro [38] suggest that BPA absorbed by the intestine is glucuronidated in the liver and excreted as BPA glucuronide in the urine. Moreover, it has been reported that the concentration of BPA in human urine samples was 110-510 pg ml −1 after ␤-glucuronidase deconjugation [13].…”

Section: Determination Of Bpa In Environmental Water and Body Fluid Smentioning

confidence: 99%

Determination of bisphenol A in river water and body fluid samples by stir bar sorptive extraction with in situ derivatization and thermal desorption-gas chromatography–mass spectrometry

Kawaguchi

Inoue

Yoshimura

et al. 2004

Journal of Chromatography B

135

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The proestrogen methoxychlor is active in a yeast oestrogenicity assay in the absence of metabolism

Cited by 5 publications

References 0 publications

Environmental Fate of Bisphenol A and Its Biological Metabolites in River Water and Their Xeno-estrogenic Activity

Environmental Fate of Bisphenol A and Its Biological Metabolites in River Water and Their Xeno-estrogenic Activity

Increased Constitutive c-Jun N-terminal Kinase Signaling in Mice Lacking Glutathione S-Transferase Pi

Determination of bisphenol A in river water and body fluid samples by stir bar sorptive extraction with in situ derivatization and thermal desorption-gas chromatography–mass spectrometry

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