Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.6.5.2 (NQO1)
 6,196 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A set of intraveous injections of 7,8,12-trimethylbenz[a]anthracene consistently elicited leukemia in more than 75% of young adult Long-Evans female rats. There was a profound reduction in the incidence of leukemia in companion groups of rats fed small amounts (1--10 mg) of Sudan III or Sudan IV prior to each injection of the carcinogenic hydrocarbon. Repeated feedings of 1 mg of Sudan III induced cumulative increases in the concentration of menadione reductase (EC 1.6.99.2) in liver, whereas protein concentration was unchanged. A single feeding of 1 mg of Sudan III prevented fatal toxicity in all members of large groups of rats injected with massive doses of 7,12-dimethylbenz[a]anthracene, but 50% of the survivors developed leukemia; unprotected rats succumbed in 1--3 days. Sudan III was not carcinogenic under the experimental conditions.
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PMID:Azo dyes prevent hydrocarbon-induced leukemia in the rat. 10 Jul 87

The effects of two carcinogens (N-acetylaminofluorene and 7, 12-dimethylbenz(a)anthracene) on the rat liver soluble D-T diaphorase are reported in this communication. The activity of the enzyme is increased in 24 hours by both compounds tested in this study.
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PMID:Rat liver post-microsomal D-T diaphorase: activation of the enzymes by two carcinogens. 40 84

The activities of NAD(P)H-dependent quinone reductase (QR) and the cytochrome P-450 monooxygenases 7-ethoxycoumarin O-deethylase (7-ECD) and 7-ethoxyresorufin O-deethylase (7-ERD) were measured in four subpopulations of murine epidermal keratinocytes (MKs) that differed in their stages of differentiation. Noninduced per cell 7-ECD and 7-ERD activities were the lowest in basal cell MKs and progressively increased as the MKs underwent differentiation. In contrast, noninduced per cell QR activities in the three less differentiated MK subpopulations were very similar to one another and greater than the activities measured in the most differentiated subpopulation. Treatment of dorsal skin with 100 nmol of dibenz[a,c]anthracene (DB[a,c]A) increased CYPIA1 mRNA abundance and elevated 7-ERD activities to similar per cell levels in all MK subpopulations. This was achieved by differential inductions (200- to greater than or equal to 1850-fold) of 7-ERD in the different subpopulations. In contrast, QR induction by DB[a,c]A was similar (less than 3-fold) in all MK subpopulations. Consequently, the expressions of noninduced QR and 7-ERD activities in skin are regulated as a function of MK differentiation. However, the distributions of the noninduced activities of these two enzymes in MK subpopulations are the exact opposite. Furthermore, the relative inducibility of 7-ERD, but not QR, in skin is also regulated as a function of epidermal differentiation.
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PMID:Differential expression of basal and hydrocarbon-induced cytochrome P-450 monooxygenase and quinone reductase activities in subpopulations of murine epidermal cells differing in their stages of differentiation. 138 68

A highly active preparation of rat liver dihydrodiol/3 alpha-hydroxysteroid dehydrogenase was obtained using a newly developed, rapid purification scheme involving affinity chromatography on Red Sepharose. Depending on the coenzyme present, the purified enzyme was found to catalyse the oxidation of dihydrodiols and steroids or the reduction of substrates with carbonyl or quinone moieties. Using a wide range of synthetic quinones derived from polycyclic aromatic hydrocarbons (PAHs), we observed a pronounced regioselectivity of the quinone reductase activity. Good substrates were the o-quinones of phenanthrene, benz(a)anthracene, chrysene and benzo(a)pyrene with the quinonoid moiety in the K-region which were reduced at rates of 1-10 mumol/min.mg enzyme. 1,4-Benzoquinone, naphthalene-1,2-quinone and benz(a)anthracene-8,9-quinone were also reduced at high rates. In contrast, alkyl-substituted quinones such as duroquinone and menadione were poor substrates for the enzyme. During the enzymatic reduction of several o-quinones, but not 1,4-benzoquinone, we observed the oxidation of large amounts of NADPH and the consumption of molecular oxygen which is indicative of a redox-cycling process. Thus, the reduction of quinones of PAHs may lead to a facilitated conjugation and excretion of these highly lipophilic compounds, but may also initiate toxic processes due to the formation of reactive oxygen species.
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PMID:Quinone reduction and redox cycling catalysed by purified rat liver dihydrodiol/3 alpha-hydroxysteroid dehydrogenase. 164 48

Modulatory effects observed due to clove administration (0.5%, 1% and 2% w/w in the diet) to Swiss albino mice for 10, 20 and 30 days in the hepatic levels of cytochrome P-450 (Cyt. P-450), cytochrome b5 (Cyt. b5), aryl hydrocarbon hydroxylase (AHH), glutathione S-transferase (GST), DT-diaphorase (DTD), acid soluble sulfhydryl (SH) content and radiation-induced malondialdehyde (MDA) formation were recorded. Enhanced GST, Cyt. b5 and SH levels were observed in all the treatment groups, excepting those maintained on a 0.5% diet for 10 days which did not show significant increase in the GST and SH levels as compared to their respective controls. Significant reduction in Cyt. P-450 and MDA levels was observed in all groups at 30 days duration. While AHH levels remained unaltered by clove administration, DTD activity was elevated by 1% and 2% clove diets at 30 days duration. An in vivo bone marrow micronucleus assay demonstrated that administration of 0.5% and 2% clove diets for 10 days neither significantly induced micronuclei nor could effectively modulate the 7, 12-dimethylbenz[a]anthracene genotoxicity in mice. The results suggest whole cloves as potential chemopreventive agents.
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PMID:Modulatory influences of clove (Caryophyllus aromaticus, L) on hepatic detoxification systems and bone marrow genotoxicity in male Swiss albino mice. 191 28

The effect of dietary intake of butylated hydroxytoluene (BHT) (0.6%) on the in vivo distribution, metabolism and DNA-binding of intragastrically administered 7,12-dimethylbenz[a]anthracene (DMBA) was evaluated. Urinary excretion of DMBA increased, blood content of metabolized DMBA increased and blood content of non-metabolized DMBA decreased for rats fed the diet containing BHT as compared to rats fed the control diet. The binding of DMBA to both liver and mammary DNA decreased for rats fed the diet containing BHT as compared to controls. The liver activities of glutathione-S-transferase (GST), epoxide hydrolase (EH) and NAD(P)H-quinone reductase (QR) increased in response to BHT feeding. However, no increase in the mammary tissue activities of these enzymes was observed. These results suggest that the ability of dietary BHT to inhibit the initiation of DMBA-induced mammary carcinogenesis partly may be due to decreased binding of DMBA to mammary DNA. This effect of BHT is not due to an increase in mammary tissue activities of GST, EH and QR, enzymes involved in carcinogen detoxification, but may involve increased liver metabolism of DMBA to products that do not bind to DNA.
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PMID:Effect of dietary butylated hydroxytoluene on the in vivo distribution, metabolism and DNA-binding of 7,12-dimethylbenz[a]anthracene. 210 65

Tannic acid inhibits the mutagenicity of several polycyclic aromatic hydrocarbons (PAHs) and their bay-region diol-epoxides. Our prior studies have shown that when applied topically to Sencar mice, tannic acid caused substantial inhibition of epidermal PAH metabolism, subsequent PAH-DNA adduct formation, and PAH-induced skin tumorigenesis (H. Mukhtar et al., Cancer Res., 48:2361-2365, 1988, and references therein). In this study the effects of tannic acid supplementation in the diet (1%, w/w, in AIN-76 diet) of Sencar mice on benzo(a)pyrene (BP) metabolism and its subsequent DNA binding and tumorigenesis in lung and forestomach were evaluated. Animals receiving a tannic acid-containing diet showed diminished aryl hydrocarbon hydroxylase and 7-ethoxy-resorufin O-deethylase activities in the forestomach and lung. Elevated glutathione S-transferase and NAD(P)H:quinone reductase activities were observed in these tissues. Maximum effects occurred after 45 days of feeding. Administration of [3H]BP p.o. to animals resulted in lower covalent binding to DNA in forestomach and lung of animals receiving tannic acid-containing diet as compared to animals receiving AIN-76 control diet. Tumor induction studies in forestomach and lung revealed significant protection against BP-induced tumorigenesis in animals fed tannic acid-supplemented diet as compared to animals fed control diet. The mice fed tannic acid-supplemented diet developed 3.3 forestomach tumors/mouse compared to 5.2 tumors/mouse in animals receiving control diet. The numbers of pulmonary tumors per mouse in animals fed tannic acid-supplemented diet and control diet were 1.6 and 3.1, respectively. Topical application of 7,12-dimethylbenz(a)anthracene to animals fed tannic acid-supplemented diet did not result in significant protection against skin tumorigenesis. However, a slight delay in the onset of skin tumor formation occurred in tannic acid-fed animals when compared to animals receiving control diet. Our data suggest that dietary supplementation with tannic acid affords protection against BP-induced forestomach and lung tumorigenesis in rodents.
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PMID:Effect of dietary tannic acid on epidermal, lung, and forestomach polycyclic aromatic hydrocarbon metabolism and tumorigenicity in Sencar mice. 250 36

Enzymes catalyzing the two-electron reduction of quinones to hydroquinones are thought to protect the cell against quinone-induced oxidative stress. Using menadione as a substrate, carbonyl reductase, a cytosolic, monomeric oxidoreductase of broad specificity for carbonyl compounds, was found to be the main NADPH-dependent quinone reductase in human liver, whereas DT-diaphorase, the principal two-electron transferring quinone reductase in rat liver, contributed a very minor part to the quinone reductase activity of human liver. Carbonyl reductase from liver was indistinguishable from carbonyl reductase previously isolated from brain (B. Wermuth, J. biol. Chem. 256, 1206 (1981] on the basis of molecular weight, isoelectric point, immunogenicity, substrate specificity and inhibitor sensitivity. The purified enzyme from liver catalyzed the reduction of a great variety of quinones. The best substrates were benzo- and naphthoquinones with short substituents, and the K-region orthoquinones of phenanthrene, benz(a)anthracene, pyrene and benzo(a)pyrene. A long hydrophobic side chain in the 3-position of the benzo- and naphthoquinones and the vicinity of a bay area or aliphatic substituent (pseudo bay area) to the oxo groups of the polycyclic compounds decreased or abolished the ability of the quinone to serve as a substrate. Non-k-region orthoquinones of polycyclic aromatic hydrocarbons were more slowly reduced than the corresponding K-region derivatives. The broad specificity of carbonyl reductase for quinones is in keeping with a role of the enzyme as a general quinone reductase in the catabolism of these compounds.
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PMID:Carbonyl reductase provides the enzymatic basis of quinone detoxication in man. 308 21

The biochemical response of rat splenic D-T diaphorase and the histochemical distribution of the enzyme NAD(P)H-NBT reductase to the action of the polycyclic hydrocarbons benz(a)pyrene, 3-methylcholanthrene, 7,12-dimethylbenz(a)anthracene and benz(a)anthracene have been studied. The four polycyclic hydrocarbons tested in this work induced the activity of both enzymes. The stimulation of the D-T diaphorase by benz(a)pyrene is dose dependent and it is partially inhibited by dicumarol. Microsomal and mitochondrial NAD(P)H dehydrogenases are not induced by any of these compounds. The study of the histochemical distribution of the NAD(P)H-NBT reductase shows also a marked increase in the staining of the enzyme which follow a specific pattern, the cells showing the highest activity are the lymphocytes located around the marginal sinus of the white pulp and around follicular arterioles, plus red pulp lymphocytes and myeloblastic cells. The cells in the germinal center show from null to very weak activity. A correlation between the biochemical induction of the soluble D-T diaphorase of the histochemical increase of the NAD(P)H-NBT reductase is attempted.
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PMID:Rat splenic D-T diaphorase and NAD(P)H-nitroblue tetrazolium reductase. Their use to assess the action of polycyclic hydrocarbons in the lymphatic system. 613 86

The action of benzo(a)pyrene, 3-methylcholanthrene and 7,12-dimethylbenzo(a)anthracene in the activity of the rat thymus D-T diaphorase (EC 1.6.99.2) and the NAD(P)H cytochrome C (EC 1.6.99.3) reductases of particulate fractions were studied in intact and adrenalectomized animals. These polycyclic hydrocarbons increased severalfold the activity of the D-T diaphorase in intact and adrenalectomized animals. The activities of the particulate enzymes were not affected by the carcinogens. Dicumarol suppresses the inducing effects of benzo(a)pyrene and adrenalectomy does not influence the inducing effects of benzo(a)pyrene and 3-methylcholanthrene. The histological distribution of the enzyme NAD(P)H-nitroblue tetrazolium reductase was studied and a marked increase in its activity in lymphocytes, macrophages and epithelial cells was found after the administration of the carcinogens.
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PMID:The influence of polycyclic hydrocarbons on the activity of NAD(P)H-dehydrogenating enzymes in rat thymus. A biochemical and histochemical study. 618 9


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