diethylstilbestrol-quinone and cumene-hydroperoxide

diethylstilbestrol-quinone has been researched along with cumene-hydroperoxide* in 2 studies

Other Studies

2 other study(ies) available for diethylstilbestrol-quinone and cumene-hydroperoxide

Article	Year
In vivo binding of diethylstilbestrol to nuclear proteins of kidneys of Syrian hamsters. Cancer letters, 1995, Apr-14, Volume: 90, Issue:2 We demonstrate here that stilbene estrogen (diethylstilbestrol) is converted to nuclear protein binding metabolite(s) both in vitro and in vivo. In vitro reaction of DES with nuclei from hamster liver or kidney in the presence of cumene hydroperoxide or NADPH revealed binding of [3H]DES in nuclear proteins (histones; nonhistones precipitable by 2% TCA, NH2; nonhistones soluble in 2% TCA, NH30). The binding was significantly inhibited by cytochromes P450 inhibitors. In an in vitro system [3H]DES quinone, one of the metabolites of DES, was able to bind to pure nonhistone proteins RNA polymerase and DNA polymerase. The binding of [3H]DES quinone to nonhistones RNA polymerase and DNA polymerase was inhibited by low molecular weight thiols, i.e. glutathione and cysteine, or thiol modifiers, such as n-ethylmaleimide, dithionitrobenzoic acid and hydroxymercuric benzoate. DES and DES metabolites inhibited transcriptional activity. In vivo [3H]DES was able to bind to nuclear proteins of hamster liver, kidneys and testes. The level of in vivo [3H]DES binding to all three types of nuclear proteins (histones, NH2, NH30) in the kidney (target organ) was two or more fold higher than that observed in the liver or testis (nontarget organs). Four nuclear NH30 proteins (mol wts.: 56, 37, 33 and 28 kDa) were irreversibly bound to [3H]DES in vivo. The in vivo binding of [3H]DES to transcriptionally active chromatin NH30 proteins also was observed. The data reported here establish that DES was able to bind to liver or kidney nuclear proteins in vitro, which was catalyzed by nuclear enzymes when fortified with an appropriate cofactor. DES quinone may be one of the protein binding metabolites. DES and DES metabolites inhibited transcriptional activity. The level of in vivo binding of [3H] DES to nuclear proteins of kidney (target organ) was double in comparison with that observed in liver or testis (nontarget organs). In vivo modifications in the chromatin proteins may be a factor in the development of DES-induced renal carcinogenesis is not clear. Topics: Animals; Benzene Derivatives; Chromatin; Chromosomal Proteins, Non-Histone; Cricetinae; Cytochrome P-450 Enzyme System; Diethylstilbestrol; DNA-Directed DNA Polymerase; DNA-Directed RNA Polymerases; Histones; Kidney; Liver; Male; Mesocricetus; NADP; Nuclear Proteins; Protein Binding; Transcription, Genetic	1995
Regulation of the formation of the major diethylstilbestrol-DNA adduct and some evidence of its structure. Carcinogenesis, 1994, Volume: 15, Issue:10 Diethylstilbestrol (DES) induces kidney tumors in hamsters. In previous studies, DES has been shown by 32P-post-labeling analysis to bind covalently to DNA in vivo and in vitro and DES-DNA adduct formation has been suggested to play a key role in DES-induced carcinogenicity. In this study, we have examined the influence of the dose of DES, age of animals and organ specificity on adduct formation in hamsters. In addition, we examined the characteristics of DES-DNA adduct formation in vitro and the structure of the major adduct. DES-DNA adducts were detected in liver and kidney of hamsters treated with at least 20 mg/kg DES. Adduct concentrations were higher at higher doses or in older compared to younger animals. The covalent binding of DES to DNA catalyzed by hamster liver microsomes required cumene hydroperoxide as cofactor, whereas with NADPH, adducts were barely detectable, presumably because the reactive metabolic intermediate DES quinone was reduced to DES. The major DES-DNA adduct formed in vitro was purified by semipreparative and analytical high pressure liquid chromatography. It is concluded that DES-DNA adducts are formed from DES quinone at very low rates in vitro and occur at low levels in vivo, even when hamsters receive very large doses of DES. The dependence of DES-DNA adduct concentrations in vitro on organic hydroperoxide cofactors required for cytochrome P450-mediated DES quinone formation indicates that stilbene-DNA adduction may occur only under conditions of oxidative stress. Topics: Animals; Benzene Derivatives; Cricetinae; Diethylstilbestrol; DNA; DNA Adducts; Drug Stability; Female; Half-Life; Male; Mesocricetus; Microsomes, Liver; NADP; Oxidation-Reduction	1994

Article

Year

In vivo binding of diethylstilbestrol to nuclear proteins of kidneys of Syrian hamsters.

Cancer letters, 1995, Apr-14, Volume: 90, Issue:2

We demonstrate here that stilbene estrogen (diethylstilbestrol) is converted to nuclear protein binding metabolite(s) both in vitro and in vivo. In vitro reaction of DES with nuclei from hamster liver or kidney in the presence of cumene hydroperoxide or NADPH revealed binding of [3H]DES in nuclear proteins (histones; nonhistones precipitable by 2% TCA, NH2; nonhistones soluble in 2% TCA, NH30). The binding was significantly inhibited by cytochromes P450 inhibitors. In an in vitro system [3H]DES quinone, one of the metabolites of DES, was able to bind to pure nonhistone proteins RNA polymerase and DNA polymerase. The binding of [3H]DES quinone to nonhistones RNA polymerase and DNA polymerase was inhibited by low molecular weight thiols, i.e. glutathione and cysteine, or thiol modifiers, such as n-ethylmaleimide, dithionitrobenzoic acid and hydroxymercuric benzoate. DES and DES metabolites inhibited transcriptional activity. In vivo [3H]DES was able to bind to nuclear proteins of hamster liver, kidneys and testes. The level of in vivo [3H]DES binding to all three types of nuclear proteins (histones, NH2, NH30) in the kidney (target organ) was two or more fold higher than that observed in the liver or testis (nontarget organs). Four nuclear NH30 proteins (mol wts.: 56, 37, 33 and 28 kDa) were irreversibly bound to [3H]DES in vivo. The in vivo binding of [3H]DES to transcriptionally active chromatin NH30 proteins also was observed. The data reported here establish that DES was able to bind to liver or kidney nuclear proteins in vitro, which was catalyzed by nuclear enzymes when fortified with an appropriate cofactor. DES quinone may be one of the protein binding metabolites. DES and DES metabolites inhibited transcriptional activity. The level of in vivo binding of [3H] DES to nuclear proteins of kidney (target organ) was double in comparison with that observed in liver or testis (nontarget organs). In vivo modifications in the chromatin proteins may be a factor in the development of DES-induced renal carcinogenesis is not clear.

Topics: Animals; Benzene Derivatives; Chromatin; Chromosomal Proteins, Non-Histone; Cricetinae; Cytochrome P-450 Enzyme System; Diethylstilbestrol; DNA-Directed DNA Polymerase; DNA-Directed RNA Polymerases; Histones; Kidney; Liver; Male; Mesocricetus; NADP; Nuclear Proteins; Protein Binding; Transcription, Genetic

1995

Regulation of the formation of the major diethylstilbestrol-DNA adduct and some evidence of its structure.

Carcinogenesis, 1994, Volume: 15, Issue:10

Diethylstilbestrol (DES) induces kidney tumors in hamsters. In previous studies, DES has been shown by 32P-post-labeling analysis to bind covalently to DNA in vivo and in vitro and DES-DNA adduct formation has been suggested to play a key role in DES-induced carcinogenicity. In this study, we have examined the influence of the dose of DES, age of animals and organ specificity on adduct formation in hamsters. In addition, we examined the characteristics of DES-DNA adduct formation in vitro and the structure of the major adduct. DES-DNA adducts were detected in liver and kidney of hamsters treated with at least 20 mg/kg DES. Adduct concentrations were higher at higher doses or in older compared to younger animals. The covalent binding of DES to DNA catalyzed by hamster liver microsomes required cumene hydroperoxide as cofactor, whereas with NADPH, adducts were barely detectable, presumably because the reactive metabolic intermediate DES quinone was reduced to DES. The major DES-DNA adduct formed in vitro was purified by semipreparative and analytical high pressure liquid chromatography. It is concluded that DES-DNA adducts are formed from DES quinone at very low rates in vitro and occur at low levels in vivo, even when hamsters receive very large doses of DES. The dependence of DES-DNA adduct concentrations in vitro on organic hydroperoxide cofactors required for cytochrome P450-mediated DES quinone formation indicates that stilbene-DNA adduction may occur only under conditions of oxidative stress.

Topics: Animals; Benzene Derivatives; Cricetinae; Diethylstilbestrol; DNA; DNA Adducts; Drug Stability; Female; Half-Life; Male; Mesocricetus; Microsomes, Liver; NADP; Oxidation-Reduction

1994