Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

High activities of aldrin epoxidase and dimethylhydrazine demethylase were found in human colon and rectum mucosa, the first being as high as in human liver biopsy specimens. Comparisons between tumorous (adenocarcinomas) and non-tumorous tissues of the same individuals revealed loss of activities in tumorous specimens. The presence of epoxidizing enzymes and demethylation of the organ-specific colon carcinogen dimethylhydrazine (DMH) in the intestinal muscosa of tumor-bearing patients implicate them with chemical carcinogenesis also in humans.
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PMID:Aldrin epoxidase and dimethylhydrazine demethylase activities in tumorous and non-tumorous tissue of the human colon and rectum. 674 34

The occurrence of kidney tumors in inbred Wistar rats as a result of dimethylnitrosamine (DMN) administration at different intervals after partial hepatectomy was studied. The schedule for DMN administration was determined on the basis of the levels of liver dimethylnitrosamine demethylase (DMN-d) at different intervals after the operation. DMN-d was 62% of the control values at 24 hours. 72% at 72 hours, and 96% at 92 hours after the operation. At these intervals a single dose of DMN (10 mg/kg body wt) was given to partially hepatectomized animals and to untreated controls. At termination, when the animals were 94 weeks old, no kidney tumors were found in the control animals, whereas 23 of 54 animals (43%) that had been given injections of DMN 24 hours after partial hepatectomy developed kidney tumors. Kidney tumor incidence was 28 or 12%, respectively, when the carcinogen was administered 72 of 92 hours after the operation. The kidney tumor incidence and the activity of liver DMN-d were inversely related.
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PMID:Production of kidney tumors in rats with low dose of dimethylnitrosamine after partial hepatectomy. 695 Jan 61

The activities of hepatic microsomal drug-metabolizing enzymes in nude mice (BALB/c-nu/nu) bearing tumors of human or nude mouse origin were studied. The content of cytochrome P-450 and the activities of cyclophosphamide oxidase, benzo[a]pyrene hydroxylase, aniline hydroxylase and benzphetamine N-demethylase were markedly decreased in tumor-bearing nude mice in accordance with previous observations in tumor-bearing rats and mice. These results indicate that decreases in the activities of hepatic microsomal drug-metabolizing enzymes are not the consequence of an immunoreactive process or cachexia.
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PMID:Decrease in the activity of hepatic microsomal drug-metabolizing enzymes in tumor-bearing nude mice. 716 May 81

Studies have been conducted on liver microsomal enzymes of B6D2F(1) mice bearing a Day 4 L1210 ascites tumor after treatment with a single intraperitoneal injection of 5-fluorouracil (FUra) alone, and in combination with either cyclophosphamide (CP), methotrexate (MTX), or methyl-CCNU (MeCCNU). FUra (200 mg/kg) alone did not alter either ethylomorphine N-demethylase, aniline hydroxylase, or neotetrazolium reductase activities as compared to untreated nontumor-bearing mice on Days 2, 4 and 6 after treatment. FUra (50 mg/kg)d plus CP (200 mg/kg) decreased neotetrazolium reductase activity 17% on Days 4 and 6 after treatment and the enzyme activity then returned to control levels on Day 8. Ethyl morphine N-demethylase and aniline hydroxylase, or neotetrazolium reductase activities on Days 1, 2, 4 and 6 after treatment. FUra (50 mg/kg) plus MeCCNU (21 mg/kg) did not affect either ethylmorphine N-demethylase or aniline hydroxylase activities on Days 1, 2, 4, 6 and 8 after treatment. However, neotetrazolium reductase activity was decreased 15% on Day 2 and then returned to control levels on Day 4. These results indicate that treatment of mice bearing the L1210 ascites tumor with an optimal single does of FUdra alone and in combination with either CP, MTX or MeCCNU does not have marked or prolonged effects on liver microsomal drug-metabolizing enzyme activities.
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PMID:Studies of the effects of treatment with 5-flourouracil alone and in combination with either cyclophosphamide, methotrexate, or methyl-CCNU on hepatic drug-metabolizing enzymes in murine L1210 leukemia. 744 41

Fluconazole is an orally active bis-triazole antifungal agent that acts by selective inhibition of lanosterol 14 alpha-demethylase, a key enzyme for maintenance of the fungal cell wall. It is not genotoxic. In a 2 year carcinogenicity study in Sprague-Dawley rats, fluconazole decreased mammary fibroadenomas in females and adrenal pheochromocytomas in males, and increased hepatic adenomas in males. The pattern of these changes is explicable in terms of a hormonal imbalance, corroborated in other studies with fluconazole in rats by changes in the weights of hormone-sensitive organs and circulating levels of 17 beta-estradiol. The decreases in mammary tumors are probably a consequence of aromatase inhibition by fluconazole at high dose levels. The tumor effects observed in this study are extremely unlikely to be of relevance to humans, since the hormone effects observed in this study do not occur in humans treated with therapeutic dose levels of fluconazole. This study illustrates the importance of seeking a mechanistic interpretation of rodent tumor findings, which may then be assessed for its relevance to the clinical use of a drug.
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PMID:Human carcinogenic risk assessment based on hormonal effects in a carcinogenicity study in rats with the antifungal agent, fluconazole. 770 62

The antimetastatic effect of GIV-A (fucoidan) and/or 5-FU was examined in an experimental model of lung metastases induced by Lewis lung carcinoma in mice. Injection of GIV-A i.p. after removal of the implanted primary tumor inhibited the development of lung metastases. Combination treatment with GIV-A and 5-FU inhibited significantly the lung metastases. The number of peritoneal macrophages, total cells and macrophages in the lung increased in mice treated with GIV-A. Binding of the third component of complement (C3) cleavage products (C3b) to the C3 receptor on peritoneal macrophages after i.v. injection of GIV-A was enhanced, as shown by the fluorescent antibody technique. Lung metastases were inhibited by i.v. injection of peritoneal macrophages activated with GIV-A. GIV-A depressed aniline hydroxylase and aminopyrine demethylase activities of the hepatic microsomal drug-metabolizing system in tumor-bearing mice. Moreover, the concentration of 5-FU in the tissues (lung, liver, kidney, spleen and blood) was increased significantly by coadministration of GIV-A. The picryl chloride-induced delayed type hypersensitivity (PC-DTH) response in mice was depressed after the implantation of tumor and treatment with 5-FU. GIV-A restored the suppression of PC-DTH by 5-FU, but did not increase the PC-DTH of normal mice. GIV-A not only enhanced the degree of spleen cell-mediated sheep red blood cell (SRBC) hemolysis (quantitative hemolysis of SRBC), the indexes of the spleen and thymus and the number of spleen cells, but also restored the suppressive effect of 5-FU. In the group receiving GIV-A, the percentages of splenic Thy1.2-, L3T4- and asialo GM1-positive cells were significantly increased as compared with the tumor-bearing mice treated with saline. Furthermore, the L3T4+/Lyt2+ ratio showed a tendency to increase, and the Lyt2+/Thy1.2+ ratio was decreased. These results suggest that the antitumor effect of GIV-A may be correlated with the changing pattern of the Thy1.2-, L3T4- and asialo GM1-positive cells, C3 activation, macrophage activation and depression of the hepatic microsomal drug-metabolizing system. These findings raise the possibility that GIV-A may have clinical value in the prevention of cancer metastasis.
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PMID:Immunological analysis of inhibition of lung metastases by fucoidan (GIV-A) prepared from brown seaweed Sargassum thunbergii. 857 81

The aim of the present studies was to describe the effect of two organohalogen pesticides: DDT and bromopropylate, on early changes in rat liver, proposed in the literature to be useful endpoints in screening of non-genotoxic hepatocarcinogens and/or liver tumor promoters. We investigated the effects on the following endpoints: hepatomegaly, mitogenesis (DNA synthesis, mitotic activity, percentage of binuclear cells) and cytochrome CYP2B1-dependent monooxygenase induction. The histological and cytochemical changes in the liver were also recorded. Male Wistar rats received bromopropylate in one, three or five daily oral doses of 125, 250, and 500 mg/kg body wt. day-1. DDT was applied as one, three, and five daily oral doses of 24 mg/kg body wt. day-1 (this dose is close to the mean hepatocarcinogenic dose in male Wistar rats: 34.1 mg/kg body wt. day-1). In the case of both pesticides the early effects observed consisted of hepatomegaly accompanied by an increase in the p-nitroanisole O-demethylase activity and hepatocyte proliferation. Hepatocyte proliferation was elevated during the total experimental period. Vacuolated cytoplasm and evident focal necrosis may suggest that the maximal increase in hepatocyte proliferation, preceding hepatomegaly, is at least partly related to a regenerative liver response to pesticides. In addition to the above-mentioned early changes, the present findings provide new evidence for the occurrence of dose-dependent abnormal mitoses (and c-mitoses) in the hepatocytes of the bromopropylate and DDT treated rats.
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PMID:Early hepatic changes induced in rats by two hepatocarcinogenic organohalogen pesticides: bromopropylate and DDT. 863 Nov 24

Garlic organosulfur compounds exert chemopreventive effects at several organ sites in rodents after administration of chemical carcinogens, possibly by inhibiting carcinogen activation via cytochrome P-450-mediated oxidative metabolism. It has been suggested that the variability in potency of tumor inhibition by garlic sulfur compounds is due to structural differences, such as the number of allyl and sulfur groups. In this study, diallyl sulfide (DAS), diallyl disulfide (DADS), and allyl methyl sulfide (AMS) were administered to acetone-treated adult male Sprague-Dawley rats by gastric gavage at a dose of 1.75 mmol/kg in cottonseed oil. After 15 hours, hepatic microsomal cytochrome P-450 activity and content were examined. The activity of p-nitrophenol (pNP) hydroxylase (E.C. 1.14.13.29) was significantly decreased by all garlic compounds, whereas benzphetamine N-demethylase and ethoxyresorufin O-deethylase activities were not changed. The activity of pNP hydroxylase was decreased to 31%, 54%, and 65% of control activity, and immunodetectable CYP2E1 protein levels were decreased in a similar manner by DAS, DADS, and AMS, respectively. Additional acetone-treated rats were given 4-methyl pyrazole, a ligand specific for CYP2E1, intraperitoneally five hours after garlic compound administration. Ten hours later, pNP hydroxylase activity was decreased to 73%, 78%, and 67% of control levels by DAS, DADS, and AMS, respectively. Further studies are needed to determine whether the variable potency of inhibition of CYP2E1 enzyme activity is related to chemopreventive efficacy of garlic sulfur compounds.
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PMID:Modulation of rat hepatic cytochrome P-450 activity by garlic organosulfur compounds. 877 67

The effects of coumarin treatment have been compared in male Sprague-Dawley CD rats, male CD-1 mice, and male Syrian hamsters. Rats were fed 0-0.75% coumarin for 1 and 4 weeks and 0-0.5% coumarin for 13 weeks, whereas mice and Syrian hamsters were fed 0-0.5 and 0-1.0% coumarin, respectively, for periods of 1, 4, and 13 weeks. In the rat, coumarin produced dose-related hepatotoxic effects which included vacuolar degeneration, apoptosis, and bile duct proliferation. These effects were particularly marked at dose levels of 0.3 and 0.5%, where liver tumors have been observed in a chronic study. Coumarin administration to rats also increased serum bilirubin content and both serum and hepatic gamma-glutamyltransferase activity. While levels of hepatic total glutathione were increased by coumarin administration, microsomal cytochrome P450 content and ethylmorphine N-demethylase activity were reduced. Such effects were either less marked or absent in the mouse and Syrian hamster. Replicative DNA synthesis was studied by implanting osmotic pumps containing 5-bromo-2'-deoxyuridine during Study Weeks 0-1, 3-4, and 12-13. In the rat, coumarin administration for 4 and 13 weeks at dose levels of 0.3 and 0.5% produced a sustained stimulation of hepatocyte replicative DNA synthesis. No such effects were observed in the mouse and Syrian hamster. These results demonstrate marked species differences in coumarin-induced hepatotoxicity. While tumor formation in the rat appears due to chronic hepatotoxicity associated with a sustained regenerative hyperplasia, such effects were not observed in the CD-1 mouse and Syrian hamster. In assessing the hazard of coumarin to humans, account needs to be taken of both levels of exposure and species differences in response.
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PMID:Comparison of the hepatotoxicity of coumarin in the rat, mouse, and Syrian hamster: a dose and time response study. 893 98

Male C57BL/6 neonates were treated on days 8 and 15 with 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP, 6.5 or 26.2 mg/kg) or dimethylnitrosamine (DMN, 2.6 or 10.5 mg/kg). No tumors were seen in PhIP-treated animals at 15 months of age. Liver and lung tumor incidences in DMN-treated animals were 67-79 and 0-7%, respectively. In comparison with data from other strains, our results indicate that (1) neonatally-treated C57BL/6 mice are resistant to the induction of liver and lung tumors by PhIP and lung tumors by DMN and (2) the susceptibility of this strain to induced liver tumors correlates with the activity of hepatic DMN N-demethylase and PhIP N-hydroxylase in the (untreated) neonates.
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PMID:Susceptibility of C57BL/6 mice to tumorigenicity induced by dimethylnitrosamine and 2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine in the neonatal bioassay. 950 Jan 98


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