Sex-dependent activities of quinone reductases in rabbits indicate higher risk of bladder cancer in the male

Mohandas, Janardanan; Chennell, Annette F.; Duggin, Geoffrey G.; Horvath, John S.; Tiller, David J.

doi:10.1093/carcin/7.3.353

Cited by 11 publications

(11 citation statements)

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“…Although CuOOH can be useful for estimating peroxidative activity it is a rather unspecific cofactor of various enzymes including monoxygenases and PHS (35,341. The major aim of this study was to assess the contribution of PHS-catalyzed oxidation to renal estrogen metabolism in hamster and in rabbit kidney, taking into account the intraorgan distribution of PHS. Our results on the metabolic activation of DES and 2-OHE1 (Tables 2 and 3) confirm the previously reported (24,25) localization of PHS activity in the medulla of rabbit kidney. Furthermore, our data show that catechol estrogens, generated as metabolites by monooxygenases, can be metabolically activated by PHS to reactive intermediates capable of covalent protein binding.…”

Section: Discussionsupporting

confidence: 92%

See 1 more Smart Citation

Multiple Pathways for the Oxidative Metabolism of Estrogens in Syrian Hamster and Rabbit Kidney

Degen

Blaich

Metzler

1990

J. Biochem. Toxicol.

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Microsomal preparations from hamster kidney, a target tissue for the carcinogenic action of stilbene-type and steroidal estrogens, catalyze the oxidative metabolism of diethylstilbestrol (DES). The formation of the major metabolite Z,Z-dienestrol and of reactive intermediates capable of protein binding were mediated by enzyme activities requiring nicotinamide-adenine dinucleotide phosphate (reduced form-NADPH), cumene hydroperoxide, or arachidonic acid (ARA). In addition, hydroxylated DES metabolites were detected in NADPH-supplemented incubations. The NADPH-dependent oxidation of DES was inhibited by SKF 525A and metyrapone. Monooxygenase-catalyzed metabolism was apparently responsible for the majority of DES oxidation in microsomes from whole hamster kidneys in vitro and this activity is preferentially localized in the kidney cortex. However, ARA-dependent, i.e., prostaglandin H synthase (PHS) mediated oxidation of DES and of the catechol estrogen 2-hydroxyestrone was demonstrated as well in the medulla of both rabbit and hamster kidney. It is proposed that monooxygenase and PHS activities act in concert in the metabolic activation of carcinogenic estrogens. This appears to apply in particular to steroidal estrogens, since catechol estrogens formed by monooxygenases are further oxidized to reactive intermediates by PHS and other peroxidatic enzymes.

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Section: Discussionsupporting

confidence: 92%

“…In the rabbit kidney, monooxygenase is localized in cortex and PHS in the medulla, and regional differences in the metabolic activation of acetaminophen, 1,3-diphenylisobenzofuran, and benzidine have been reported (24,25). For hamster kidney, monooxygenase-mediated metabolism of DES has been studied with cortical slices (26,27).…”

Section: Introductionmentioning

confidence: 99%

Multiple Pathways for the Oxidative Metabolism of Estrogens in Syrian Hamster and Rabbit Kidney

Degen

Blaich

Metzler

1990

J. Biochem. Toxicol.

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“…An important question is the possible consequences of different activities of QAO in human tumors compared to normal tissue and the effect of smoking and alcohol use. QAO is thought to be one of a series of enzymes that protect against chemical carcinogenesis (Mohandas et al, 1986;Prochaska et al, 1985;Talalay and Benson, 1982). This suggestion is based on the observation that a number of carcinogens are metabolized to quinone intermediates, some of which may be the ultimate carcinogen (Lesko and Lorentzen, 1985;Wislocki et al, 1976).…”

Section: Discussionmentioning

confidence: 99%

“…However, it has been claimed that simple hydroquinones are less reactive than semiquinone radicals and more easily eliminated from the cell as conjugates (Lind, 1985). QAO has been reported to protect cells against quinoneinduced cell necrosis (Benson et al, 1980;Lind et al, 1978;Momson et al, 1984;Thor et al, 1982) and carcinogenicity (Ames, 1983;Mohandas et al, 1986;Prochaska et al, 1985;Talalay and Benson, 1982) by reducing the concentration of free quinone available for single-electron reduction.…”

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confidence: 99%

Cytosolic NAD(P)H:(Quinone‐acceptor)oxidoreductase in human normal and tumor tissue: Effects of cigarette smoking and alcohol

Schlager

Powis

1990

Intl Journal of Cancer

226

159

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NAD(P)H:(quinone-acceptor)oxidoreductase (QAO), previously known as DT-diaphorase, catalyzes the reduction of quinones to hydroquinones. Enhanced activity of the enzyme has been suggested to protect cells against the cellular toxicity and carcinogenicity of quinones, but may activate some cytotoxic anti-tumor quinones. Cytosolic levels of QAO, carbonyl reductase (CR) and total quinone reductase activity have been measured in normal and tumorous human tissues. QAO was the major component of the total cytosolic quinone reductase activity in all the tissues investigated. CR represented 10 to 28% of the total cytosolic quinone reductase activity in normal tissue. Normal tissue QAO was high in the stomach and kidney, and lower in the lung, liver, colon and breast. Primary tumor from lung, liver, colon and breast had elevated levels of QAO compared to normal tissue, while tumor from kidney and stomach had lower levels. CR was not significantly altered in tumor tissue, except in the case of lung and colon tumor which showed an increase compared to normal tissue. A major determinant of the variability of human lung tumor QAO was the cigarette-smoking history of the donor. Non-smokers and past smokers had high levels of tumor QAO compared to normal tissue. Smokers had levels of tumor QAO that were not significantly different from those of normal tissue QAO. Smokers had a small increase in normal lung QAO compared to non-smokers. Alcohol use was associated with an increase in lung tumor QAO but had no effect on QAO in normal lung. The function of QAO in tumors is not known but the elevated activity of QAO in some tumors and the apparent depressant effect of smoking could influence the response of these tumors to quinone drugs or toxic agents that are metabolized by QAO.

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“…3,4 They also exhibit high biological activity as antimalarial, antifungal, antitumor and antibacterial agents. [5][6][7][8][9] The p-chloranil containing chlorine atoms and a pair of carbonyl groups is a quite reactive compound. Therefore a large number of p-benzoquinone derivatives are synthesized from p-chloranil.…”

Section: Introductionmentioning

confidence: 99%

The Synthesis of Novel Mono(alkoxy)-, Tris(thio)- and Tetrakis(thio)-Substituted Quinones from the Reactions of p-Chloranil with Various S-Nucleophiles

2009

Bulletin of the Korean Chemical Society

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The tetrakis(thio)-substituted-1,4-benzoquinone products 4a-e, 6, 7, and the mono(alkoxy)-tris(thio)-substituted-1,4-benzoquinone products 5a-e and 8a-e were synthesized from the reactions of p-chloranil with some thiols and mixture of two different thiol compounds in alcohol in the presence of Na2CO3 at room temperature. The structures of the novel S,S,S,S-and S,S,S,O-substituted products, which were obtained by the reactions of p-chloranil as a starting compound with n-propanethiol, n-pentanethiol, n-decanethiol, n-dodecanethiol, 2-methyl-2-propanethiol, and mixture of n-decanethiol and n-cyclohexanethiol as S-nucleophiles, were characterized by spectroscopic methods.

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Sex-dependent activities of quinone reductases in rabbits indicate higher risk of bladder cancer in the male

Cited by 11 publications

References 0 publications

Multiple Pathways for the Oxidative Metabolism of Estrogens in Syrian Hamster and Rabbit Kidney

Multiple Pathways for the Oxidative Metabolism of Estrogens in Syrian Hamster and Rabbit Kidney

Cytosolic NAD(P)H:(Quinone‐acceptor)oxidoreductase in human normal and tumor tissue: Effects of cigarette smoking and alcohol

The Synthesis of Novel Mono(alkoxy)-, Tris(thio)- and Tetrakis(thio)-Substituted Quinones from the Reactions of p-Chloranil with Various S-Nucleophiles

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