Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: CAS:7732-18-5 (water)
 694,341 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The occurrence of inflammatory processes and of cancer in the human respiratory tract is intimately associated. One of the major factors in this is probably the recruitment of and stimulated activity of polymorphonuclear leukocytes (PML) in conjunction with the ability of these cells to convert various carcinogens to their ultimate active metabolites. In this study, we demonstrate that nitrite and sulfite, the major dissolution products of the environmental pollutants nitrogen dioxide and sulfur dioxide in water enhance the metabolic activation of trans-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene (BP-7,8-dihydrodiol), the proximal carcinogen of benzo[a]pyrene, to trans-7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE) and tetraols, the corresponding hydrolysis products, in human PML prestimulated with 12-O-tetradecanoylphorbol-13-acetate. Nitrite was more efficient than sulfite in stimulating the formation of reactive intermediates of BP-7,8-dihydrodiol in PML that covalently bind to extracellular DNA and, in particular, to intracellular proteins. The mechanism by which sulfite stimulates the metabolism of BP-7,8-dihydrodiol most probably involves the intermediate formation of a sulfur trioxide radical anion (SO3.-) the subsequent formation of the corresponding sulfur peroxyl radical anion (.OOSO3-) in the presence of oxygen. The mechanism underlying the stimulatory action of nitrite is less clear but the major pathway seems to involve myeloperoxidase. These results offer an explanation for the increased incidence of lung cancer in cigarette smokers living in urban areas. The major glutathione transferase (GST) isoenzyme in human PML is GST P1-1, a Pi-class form. The GST activity of PML was found to be inversely correlated with the extent of binding of BP-7,8-dihydrodiol products to exogenous DNA. These results suggest that individuals exhibiting high GST-activity in the PML may be better protected against the type of carcinogenic dealt with in this study.
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PMID:Stimulatory effects of sulfur and nitrogen oxides on carcinogen activation in human polymorphonuclear leukocytes. 782 Dec 91

The potential carcinogenicity of coffee and related compounds was examined using a medium-term liver bioassay based on the induction of glutathione S-transferase placental form (GST-P)-positive foci in F344 rats. A total of 230 males were initially injected with diethylnitrosamine (200 mg/kg body weight, ip) or saline as controls and 2 wk later were fed on diet or drinking water supplemented as follows for 6 wk: 5% regular instant coffee; 5% decaffeinated instant coffee; freshly brewed coffee, 8 g in 140 ml water; 0.1% caffeine, 0.2% methylglyoxal, 0.2% glyoxal; or 0.3% theophylline in the drinking water (w/v); and 0.4% theobromine in the diet (w/w). All rats were subjected to two-thirds partial hepatectomy at wk 3 and killed at wk 8. The resultant values for GST-P-positive hepatic focus induction were slightly increased with methylglyoxal and decreased with glyoxal and theobromine compared with the corresponding controls. Although the increase in number of foci for methylglyoxal was statistically significant at P < 0.05, the value was within the historical control levels. Regular and decaffeinated instant coffee as well as fresh-brewed coffee, caffeine and theophylline exerted no effects on focus development. Thus, the coffee-related compounds examined demonstrated no obvious enhancing potential, and it is therefore concluded that coffee and its main constituents are not carcinogenic for the rat liver.
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PMID:Analysis of the potential carcinogenicity of coffee and its related compounds in a medium-term liver bioassay of rats. 782 71

We investigated the effect of potato extracts and 16,16-dimethyl prostaglandin E2 (DiPGE2) on the induction of glutathione S-transferase P-positive (GST-P+) altered hepatic foci in newborn Sprague-Dawley rats given single treatment with 60Co gamma irradiation and diethylnitrosamine (DEN) alone or in sequential combination. Intraperitoneal injection of 0.15 mumol/g body weight of DEN 1 hour after gamma radiation significantly increased the frequencies of GST-P+ hepatic foci compared to DEN or gamma radiation alone and DEN injection 1 hour before irradiation (p < 0.001). Potato extract was given at a dose of 2 mg/ml in drinking water for 3 weeks and DiPGE2 given at a dose of 10 micrograms/mouse 30 minutes before irradiation. Potato extracts and DiPGE2 decreased significantly the number (p < 0.001), area (p < 0.001) and Dmax (p < 0.05) of GST-P+ hepatic foci compared to the corresponding control. These results suggest that potato extracts and DiPGE2 have radio-protective potential and further studies for underlying mechanisms will be necessary.
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PMID:Protective effects of potato extracts and 16,16-dimethyl prostaglandin E2 on the induction of hepatic foci by cotreatment of gamma radiation and diethylnitrosamine. 784 37

The effects of acute and chronic exposure to lead on glutathione S-transferase (GST) isoforms were determined in developing kidney in the rat. The ontogeny of glutathione S-transferase isoforms was characterized as were the effects of depletion of dietary calcium on glutathione S-transferase isoform profiles in control and lead-treated rats. In the acute exposure experiments, rats of 14 and 50 days of age received three daily injections of lead acetate (114 mg/kg) and in the chronic exposure studies, rats received lead acetate at doses ranging from 50 to 500 ppm in their drinking water. Lead acetate administration in these chronic studies began 1 day after conception. Acute and chronic lead exposure had similar effects, causing increases in all but one glutathione S-transferase isoform (Yb3); these increases were markedly exacerbated by dietary calcium depletion. In all lead paradigms, GST subunits Yb1 and Yp showed the largest increases--greater than 25-fold in rats fed a low-calcium diet. GST subunit Yb3 showed small increases in the 14-day acute lead and the 4 week low-calcium animals and did not increase in other groups. Lead-related increases in GSTs were partially reversed by transferring animals previously receiving lead to lead-free water for a 4-week period. Kidneys of rats fed the low-calcium diet did not have detectable GST Yk, but in rats on this low-calcium diet that received 500 ppm lead; this GST isoform was found at levels comparable to those in control rats fed lab chow.
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PMID:Effects of lead administration on developing rat kidney. I. Glutathione S-transferase isoenzymes. 787 82

The effects of chronic lead administration on renal function and cytoarchitecture and on the immunohistochemical localization of glutathione S-transferase (GST) isoenzymes were determined. Pregnant rats were given 250 ppm lead acetate in drinking water from conception until weaning and mothers and pups received 500 ppm of lead acetate from weaning until termination at either 3 or 7 weeks of age. Light and electron microscopic studies after 3 weeks of lead administration showed tubular injury with frequent mitoses noted in proximal tubular cells and, after 7 weeks of treatment, interstitial fibrosis, characteristic intranuclear inclusions, and tubular injury characterized by both nuclear and cytoplasmic pleomorphism. Rats treated with lead for 7 weeks showed significantly lower body weights and creatinine clearances than age-matched control animals. Immunohistochemical studies of glutathione transferase subunits in control rats showed unique isoform localization in each segment of the nephron; treatment with lead caused large increases in immunoreactive protein of Yc, Yk, Yb1, and Yp GST subunits in proximal tubules. No increases in the antioxidant enzymes copper-zinc superoxide dismutase, catalase, and glutathione peroxidase were found in lead-treated rats, but there was a diffuse lead-related increase in immunoreactive protein for manganese superoxide dismutase throughout the renal cortex. Our results demonstrate large lead-induced increases of specific isoforms of glutathione S-transferase in specific kidney cell types and show that these increases preceded irreversible renal damage.
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PMID:Effects of lead administration on developing rat kidney. II. Functional, morphologic, and immunohistochemical studies. 787 83

Arsenic (As) is environmentally ubiquitous and an epidemiologically significant chemical related to certain human cancers. Dimethylarsinic acid (cacodylic acid; DMA) is one of the major methylated metabolites of ingested arsenicals in most mammals. To evaluate the effects of DMA on chemical carcinogenesis, we conducted a multiorgan bioassay in rats given various doses of DMA. One-hundred twenty-four male F344/DuCrj rats were divided randomly into 7 groups (20 rats each for groups 1-5; 12 rats each for groups 6 and 7). To initiate multiple organs and tissues, animals in groups 1-5 were treated sequentially with diethylnitrosamine (100 mg/kg body weight, i.p., single dose at the commencement) and N-methyl-N-nitrosourea (20 mg/kg body weight, i.p., 4 times, on days 5, 8, 11, and 14). Thereafter, rats received 1,2-dimethylhydrazine (40 mg/kg body weight, s.c., 4 times, on days 18, 22, 26, and 30). During the same period, the animals were sequentially administered N-butyl-N-(4-hydroxybutyl)nitrosamine (0.05% in the drinking water, during weeks 1 and 2) and N-bis(2-hydroxypropyl)nitrosamine (0.1% in the drinking water, during weeks 3 and 4; DMBDD treatment). After a 2-week interval, groups 2-5 were given 50, 100, 200, or 400 ppm DMA, respectively, in the drinking water. Groups 6 and 7, which were not given DMBDD treatment, received 100 and 400 ppm DMA during weeks 6-30. All rats were killed at the end of week 30. In the initiated groups (groups 1-5), DMA significantly enhanced the tumor induction in the urinary bladder, kidney, liver, and thyroid gland, with respective incidences in group 5 (400 ppm DMA) being 80, 65, 65, and 45%. Induction of preneoplastic lesions (glutathione S-transferase placental form-positive foci in the liver and atypical tubules in the kidney) was also significantly increased in DMA-treated groups. Ornithine decarboxylase activity in the kidneys of rats treated with 100 ppm DMA was significantly increased compared with control values (P < 0.001). In conclusion, DMA is acting as a promoter of urinary bladder, kidney, liver, and thyroid gland carcinogenesis in rats, and we speculate that this may be related to cancer induction by As in humans.
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PMID:Cancer induction by an organic arsenic compound, dimethylarsinic acid (cacodylic acid), in F344/DuCrj rats after pretreatment with five carcinogens. 788 21

Catechin and dietary turmeric (Curcuma longa) were used as chemopreventive agents in benzo[a]pyrene induced forestomach tumors in Swiss mice and methyl-(acetoxymethyl)-nitrosamine induced oral mucosal tumors in Syrian golden hamsters. Catechin in drinking water and dietary turmeric significantly inhibited the tumor burden and tumor incidence in both tumor models. The induction of oral tumors in golden hamsters was delayed by catechin and dietary turmeric. Adjuvant chemoprevention utilising both catechin and dietary turmeric inhibited both the gross tumor yield and burden more effectively than when compared to individual components in both tumor models. A single i.p. injection of catechin to male Swiss mice induced increased forestomach and hepatic glutathione S-transferase (GST) activity when compared to controls. These findings suggest that catechin and turmeric which are regularly consumed natural products, are effective in mice or golden hamsters as chemopreventive agents.
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PMID:Adjuvant chemoprevention of experimental cancer: catechin and dietary turmeric in forestomach and oral cancer models. 789 28

The effect of somatostatin on hepatocarcinogenesis induced by N-nitrosomorpholine (NNM) was investigated in male Sprague-Dawley rats. Rats were given drinking water containing NNM for 8 weeks and s.c. injections of 200 micrograms/kg body wt of somatostatin every other day from the beginning of the experiment until the end of week 16. Pre-neoplastic and neoplastic lesions staining for gamma-glutamyl transpeptidase (GGT) or placental type glutathione-S-transferase (GST-P) were examined histochemically. Administration of somatostatin for 16 weeks resulted in significant reduction in the percentage volume of GGT-positive and GST-P-positive lesions. The incidence, number and size of hepatocellular carcinomas were significantly less in rats treated with somatostatin than in untreated rats. Administration of somatostatin significantly decreased the labeling indices of pre-neoplastic lesions and adjacent liver. These findings indicate that somatostatin inhibits hepatocarcinogenesis and that this effect may be related to its effect in decreasing cell proliferation in pre-neoplastic lesions.
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PMID:Inhibition by somatostatin of hepatocarcinogenesis induced by N-nitrosomorpholine in Sprague-Dawley rats. 790 4

The inducing activities of two alkaloids, strychnine and brucine, on the hepatic drug metabolizing enzymes were studied in rats. Administration of strychnine in the drinking water to rats significantly increased the hepatic microsomal activities of benzphetamine N-demethylation, strychnine 2-hydroxylation and testosterone hydroxylations at positions 16 alpha and 16 beta. These results together with that of immunostaining of microsomal proteins revealed that strychnine is a potent inducer of CYP2B1 and 2B2. The comparable induction of CYP2B1/2 was observed by brucine treatment with less toxic effect. Although this inducer increased CYP2B cytochrome P450s (P450s) to the maximum levels after 4 consecutive days of administration, the maximal increase by strychnine was attained after 3 days of administration. Immunoblotting experiment suggested that significant proteolysis of CYP2B1 occurs during treatment by strychnine and brucine. These alkaloids exhibited no ability to induce the activities of testosterone hydroxylations at positions 2 alpha, 6 beta and 7 alpha, benzo[a]pyrene 3-hydroxylation and aniline hydroxylation. In addition to the CYP2B P450, strychnine and brucine induced glutathione S-transferase toward 1-chloro-2,4-dinitrobenzene and UDP-glucuronosyltransferase toward 4-nitrophenol. On the other hand, the glucuronidations of 4-hydroxybiphenyl and morphine were not enhanced by alkaloid treatments. These results indicated that strychnine and brucine cause phenobarbital-like induction of the P450 enzyme, but show a different profile from phenobarbital in the induction of UDP-glucuronosyltransferase.
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PMID:Strychnine and brucine as the potent inducers of drug metabolizing enzymes in rat liver: different profiles from phenobarbital on the induction of cytochrome P450 and UDP-glucuronosyltransferase. 790 30

The synergism of two carcinogenic aromatic amines with different tissue specificities was studied at the level of initiation in Wistar rats. Gamma-glutamyl transpeptidase and glutathione S-transferase P were used as markers for preneoplastic foci in liver. 2-Acetylaminofluorene (AAF) is a complete rat liver carcinogen, whereas trans-4-acetylaminostilbene (AAS) produces ear duct tumors quite selectively, but also acts as a strong initiator in rat liver. When these carcinogens were administered sequentially as two doses of each or simultaneously as four doses of a mixture to neonate animals, which then were treated with phenobarbital in the drinking water for promotion, the initiating activity was additive. When these chemicals were given to young adult animals within 4 weeks in two series of four doses, followed by partial hepatectomy and phenobarbital in the drinking water, the number of preneoplastic foci was greater in groups which had received AAS in both series or in the second series after AAF than in those groups which had received only AAF or AAF in the second series. The average size of foci depended clearly on the sequence in which the two carcinogens were administered. The foci were larger when AAF was given after AAS. The results support the notion that AAS is a strong initiator in rat liver, and that AAF, which is a complete liver carcinogen, has promoting properties under certain circumstances in addition to its initiating properties. The two carcinogens seem to produce the initiating lesions independently but the extent of initiation is additive in this model situation. The simplified neonatal rat liver model appears to be particularly suitable for investigating initiating properties and is proposed for studies of synergistic effects of genotoxic chemicals on the initiation stage, independent of organotropism. It avoids a number of complicating factors related to treatment schedule, forced proliferation rate and toxicity in other models.
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PMID:Synergistic effects of trans-4-acetylaminostilbene and 2-acetylaminofluorene at the level of tumor initiation. 791 6


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