Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0001430 (adenoma)
 21,222 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Biochanin A was studied for its capacity to inhibit benzo(a)pyrene (BP) induced neoplasia in female Swiss Webster mice. To investigate the effect of biochanin A on the initiation step, biochanin A (500 mg/kg) was administered orally 48 hours prior to BP (3 mg/mouse), which was also given orally. This sequence of biochanin A and BP administration was repeated once a week for a total of 4 weeks. At 26 weeks after the last treatment, all the mice were sacrificed. To investigate the effect of biochanin A on the promotion step, a single subcutaneous injection of 0.5 mg of BP was given within 24 hours after birth, and biochanin A (0.125 mg/mouse) was injected intraperitoneally 3 times a week for 6 weeks after weaning. In the initiation protocol, the concomitant administration of biochanin A showed significant inhibition of the mean number of lung tumors (P less than 0.001) and the incidence of carcinoma of the forestomach (P less than 0.02). In the promotion protocol, biochanin A significantly inhibited the incidence (P less than 0.01) and the multiplicity (P less than 0.001) of pulmonary adenoma, compared with the group treated with BP alone. These results suggest that biochanin A inhibitory potential in the initiation, as well as in the promotion step of BP carcinogenesis in female Swiss-Webster mice.
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PMID:Inhibitory effects of biochanin A on benzo(a)pyrene induced carcinogenesis in mice. 139 95

The effects of indole-3-carbinol (I3C) on lung neoplasia induced by the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) were assessed in an A/J mouse pulmonary adenoma bioassay. Mice were administered corn oil or I3C (25 or 125 mumol/mouse/day) by gavage for 4 consecutive days. Two h after the final pretreatment, mice were administered a single dose of NNK (10 mumol/mouse) i.p. Pulmonary adenomas were quantitated 16 wk after NNK dosing. Mice pretreated with corn oil developed 10.7 tumors/mouse; I3C pretreatment at either dose level inhibited tumor multiplicity by approximately 40%. The effects of I3C on NNK-induced DNA methylation in the lungs and livers of A/J mice were assessed using the same dosing regimen as in the bioassay. Both dose levels of I3C inhibited pulmonary O6-methylguanine formation by at least 50%, but enhanced hepatic DNA methylation at 2 or at 6 h after NNK administration. The effects of I3C pretreatment on NNK metabolism were also investigated. Hepatic microsomes of I3C-pretreated mice showed increased formation of alpha-hydroxylation products, while no significant effect of I3C pretreatment was observed in pulmonary microsomes. The effects of I3C on [5-3H]NNK disposition were also evaluated. I3C pretreatment produced lower levels of total radioactivity in the lung when compared with controls. Additionally, lower proportions of NNK and its carcinogenic metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol were found in the lungs of I3C-pretreated mice. These results demonstrate that I3C inhibits NNK-induced lung neoplasia in A/J mice and suggest that the basis of this inhibition is the decrease in O6-methylguanine formation in A/J lung caused by I3C pretreatment. This decrease in lung DNA methylation appears to be due to the decreased bioavailability of NNK and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol in the lungs of I3C-treated mice which, in turn, may be a result of increased metabolic alpha-hydroxylation of NNK by the liver.
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PMID:Effects of indole-3-carbinol on lung tumorigenesis and DNA methylation induced by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and on the metabolism and disposition of NNK in A/J mice. 232 87

A newborn mouse (BLU:Ha) lung adenoma bioassay demonstrated that 6-nitrochrysene was a highly potent tumorigen. It induced 100% incidence of lung tumors and a 150-fold increase in their number (20.84 tumors/mouse) at the lowest dose level tested (total dose: 38.5 micrograms/mouse). 70% of the 6-nitrochrysene treated mice had malignant lung tumors (adenocarcinomas). Lymphomas and nodular hyperplasia of the liver were also observed in treated, but not control, animals. The tumorigenicity of 6-nitrochrysene relative to other polynuclear aromatic hydrocarbons and their mononitro-derivatives has been discussed.
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PMID:6-Nitrochrysene is a potent tumorigen in newborn mice. 400 66

Previous results in various in vitro systems suggest that prostaglandin endoperoxide synthetase (PES) could serve as either an alternative or an additional enzyme to the cytochrome P-450-dependent monooxygenases for the formation of mutagenic, cell-transforming, and DNA-binding metabolites of carcinogens. To test this hypothesis in vivo, we examined the effect of PES inhibitors on benzo(a)pyrene (BP)-induced pulmonary adenoma and BP metabolite:DNA adduct formation in A/HeJ mice. Animals were treated with a dosage regimen of aspirin which inhibited PES but had no effect on the cytochrome P-450-dependent oxidation of 7,8-dihydrodihydroxybenzo(a)pyrene. Aspirin did not significantly alter the number of pulmonary adenomas per mouse at either dose of BP (6.0 and 3.0 mg per mouse, administered twice, 2 weeks apart). In addition, aspirin treatment did not depress the in vivo formation of BP metabolite:DNA adducts in lung or liver at either dose of BP (6.0 and 0.06 mg/mouse). The lower dose of BP was used in the adduct study to assess the effect of aspirin at a more environmental exposure level of BP. Treatment with indomethacin, another PES inhibitor, also did not reduce the pulmonary BP metabolite:DNA adduct levels. The failure of PES inhibitors to reduce the number of pulmonary adenomas and BP metabolite:DNA adduct levels suggests that cooxidation of BP during prostaglandin biosynthesis may not play a significant role in BP-induced pulmonary adenomas.
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PMID:Effect of aspirin and indomethacin on the formation of benzo(a)pyrene-induced pulmonary adenomas and DNA adducts in A/HeJ mice. 630 76

A 24 week lung adenoma bioassay using newborn mice was employed to determine the tumorigenicity of fluoranthene, a common environmental polynuclear aromatic hydrocarbon. A 6.5-fold elevation of lung tumor incidence (58%) and a 12-fold increase in numbers (1.08 tumors/mouse) was observed in animals treated with the highest dose (3.5 mg/mouse), but no increase in tumor incidence was induced by 700 micrograms/mouse. Benzo[a]pyrene, used as a positive control at a comparatively low dose (280 micrograms/mouse), was highly potent, inducing lung tumors in 94% of the animals and elevating their number by 44-fold (4.0 tumors/mouse). Most of the mice treated with the highest dose of benzo[a]pyrene (1.4 mg/mouse) died with massive injection site sarcomas. Male mice, surviving for 24 weeks in fluoranthene and benzo[a]pyrene treatment groups that developed lung tumors, had 2- to 3-fold more tumors than comparably treated females. This is the first reported evidence of tumorigenicity of fluoranthene. The significance of these findings in terms of bioassay sensitivity and the implications regarding human health have been discussed.
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PMID:Tumorigenicity of fluoranthene in a newborn mouse lung adenoma bioassay. 648 52

Ornithine decarboxylase activity and polyamine concentrations were determined in the lungs of mice from 0 to 20 h after treatment with 12-O-tetradecanoylphorbol-13-acetate (17.7 nmol in 0.2 ml acetone/mouse). In CFLP mice, which responded to carcinogen with development of lung-adenomas, a single topical application of TPA to hairless mouse skin increased ornithine decarboxylase activity in the lung. In contrast, in C3H/He-mg mouse strain, which were resistant to lung-adenoma production, TPA application did not increase ODC activity of the lungs.
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PMID:Effect of 12-O-tetradecanoylphorbol-13-acetate on polyamine metabolism in mice sensitive and resistant to lung-adenoma. 661 64

We have examined phospholipid-transfer activities in cytosols from rat and mouse whole lung, isolated rat alveolar type II cells and alveolar type II cell-derived mouse pulmonary adenomas. We report an enrichment in phosphatidylcholine and phosphatidylglycerol (but not phosphatidylinositol) protein-catalysed transfer in the type II cell and adenoma cytosols compared with the whole-lung cytosols. The activities from these cytosols were resolved using column chromatofocusing, which clearly demonstrated the presence of a phosphatidylcholine-specific transfer protein in each of the four tissues. In addition, two proteins (rat) or three proteins (mouse) catalysing both phosphatidylcholine and phosphatidylglycerol transfer were resolved from whole lung, whereas in both the rat isolated alveolar type II cells and the mouse type II cell-derived adenomas one of these less specific proteins is not present.
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PMID:Phospholipid-transfer activities in cytosols from lung, isolated alveolar type II cells and alveolar type II cell-derived adenomas. 666 Nov 89

In earlier studies, it was found that the new antioxidant, MTDQ-DA ((6,6-methylene-bis)2,2-dimethyl-4-methane-sulphonic acid sodium salt-1,2-dihydroquinoline) (Patent No. 3172) prevented in vivo nitrosation and the acute hepatotoxicity of morpholine plus sodium nitrite in rats. The aim of the present experiments was to examine whether MTDQ-DA could decrease the frequency of tumours induced by simultaneous administration of morpholine and nitrite in the lung adenoma assay. Forty CFLP mice were used in each group and they were killed 8 months after treatment. In group A, treated with 1000 mg/kg morpholine i.g., and in Group B (untreated control) a similar frequency of lung adenomas could be observed (0.13 adenomas/mouse). After the combined i.g. treatment in Group C (MOR, 1000 mg/kg + nitrite, 125 mg/kg), the incidence of lung adenomas was found to be 16.58/mouse. A single dose of MTDQ-DA (500 mg/kg) added to the group C treatment reduced the lung adenoma frequency to 2.47/mouse (Group D). As MTDQ-DA shows neither toxic nor mutagenic effects and inhibits the in vivo nitrosation in both hepatotoxicity and lung adenoma assays, it may be considered to be a potential food additive.
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PMID:Inhibition by an antioxidant of the carcinogenic effect of nitrosomorpholine formed in vivo. 714 73

Cyclopenta[cd]pyrene (CPP) is a ubiquitous cyclopenta-fused polycyclic aromatic hydrocarbon. CPP is highly genotoxic in bacterial and mammalian systems inducing gene mutations, sister chromatid exchanges and morphological transformation. CPP is a mouse skin carcinogen, a mouse skin tumor initiator and induces pulmonary tumors in newborn mice. We have examined the tumorigenic activity of CPP in strain A/J mice, have determined the formation and persistence of CPP-induced DNA adducts in lung tissue, and analyzed the mutational spectrum in the Ki-ras oncogene from CPP-induced tumors. CPP dissolved in tricaprylin was administered by i.p. injection to male A/J mice (20 mice/dose) at 0, 10, 50, 100 and 200 mg/kg. Animals were killed 8 months later and the lungs removed, fixed, and surface adenomas enumerated. CPP proved to be highly tumorigenic in A/J mice in terms of inducing lung adenomas. The observed tumor multiplicities (lung adenomas/mouse) were: 97.7 +/- 28.7 at 200 mg/kg, 32.8 +/- 15.4 at 100 mg/kg, 4.63 +/- 2.11 at 50 mg/kg and 0.58 +/- 0.82 at 10 mg/kg. Tricaprylin-treated controls produced 0.60 +/- 0.58 lung adenomas/mouse. Groups of mice treated under the same dosing conditions as those in the tumor studies were killed 1, 3, 7, 14 and 21 days after treatment. The lungs were removed, and the DNA was subjected to DNA adduct analysis by the 32P-postlabeling method. Total CPP-DNA adducts in mouse lung peaked at day 3 with 5870 amol CPP adducts/micrograms DNA after a single dose of 200 mg/kg. DNA adduct levels decreased to 1800 amol CPP adducts/micrograms DNA at day 21. Qualitative DNA adduct analysis revealed four major adducts and one minor adduct. Co-chromatography of the lung DNA from CPP-treated mice with calf thymus DNA treated with CPP-3,4-oxide indicated that all DNA adducts were oxide derived and comparison with CPP-3,4-oxide-treated polydeoxyguanylic acid suggests that almost all of these adducts are CPP-3,4-oxide-2'-deoxyguanosine adducts. Ki-ras codon 12 mutation analysis of the DNA from tumors taken from the 100 and 200 mg/kg CPP dose groups demonstrated the following patterns: GGT-->CGT (50%); GGT-->GTT (15%); GGT-->TGT (25%); GGT-->GAT (10%). We conclude that CPP is highly tumorigenic in the A/J mouse lung adenoma model, being five times more active than benzo[a]pyrene. This is unlike the result of CPP as a mouse skin tumorigen or tumor initiator in which CPP is considerably less potent than benzo[a]pyrene.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Cyclopenta[cd]pyrene-induced tumorigenicity, Ki-ras codon 12 mutations and DNA adducts in strain A/J mouse lung. 814 68

We used the C57BL/6J-APC(Min)/+ mouse (Min mouse) to evaluate the chemopreventive effects of R-flurbiprofen (R-FB), the noncyclooxygenase-inhibiting enantiomer of FB. Weanling Min mice were administered 6 weeks of oral treatment with R-FB using 2.5-25 mg/kg of R-FB once per day (q.d.), 2.5-10 mg/kg of R-FB twice per day (b.i.d.), and 5 mg/kg of R-FB b.i.d. challenged with a high saturated fat diet. At necropsy we determined tumor and ulcer numbers, tumor size, and plasma levels of R- and S-FB. A linear dose response was observed from 2.5 to 10 mg/kg of R-FB, regardless of whether the drug was administered as a single or divided dose. Reductions in tumor number were significant (P < or = 0.02) for doses of R-FB from 2.5 to 25 mg/kg/day. A dose of 5 mg/kg R-FB b.i.d. was able to overcome the doubling in tumor number associated with the high saturated fat diet. At 20 and 25 mg/kg/day R-FB, we obtained the maximum response with up to 90% inhibition of total tumor number. At these doses, however, there was toxicity and animal deaths. This toxicity was associated with ulceration, presumably resulting from the in vivo epimerization of R- to S-FB that occurs in the mouse. Thus, we evaluated the oral pharmacokinetics of R-FB and its conversion to S-FB in wild-type mice. These kinetics experiments revealed inversion rates of 7.3 and 11.0% for the 2.5 and 10 mg/kg R-FB doses, respectively. S-FB administered alone (0.5 and 2.0 mg/kg q.d.), in doses mimicking the concentrations of S-FB associated with the R to S epimerization of the doses of R-FB used in our experiments, had little or no antitumor efficacy (P > 0.05). Thus, we conclude that R-FB itself, not the S-FB resulting from epimerization in the mouse, inhibits adenoma formation in the Min mouse. In humans, where there is no R to S epimerization, it is possible that larger doses of R-FB can be used without causing cyclooxygenase inhibition and its resulting ulcerogenicity and other side effects. To assess the effect of R-FB on established adenomas, we allowed 40 Min mice to remain untreated until 70 days of age (the time of necropsy in the previous experiments) and then treated them for an additional 42 days with 10 mg/kg R-FB q.d. or 5 mg/kg R-FB b.i.d.. Both drug-treated groups demonstrated tumor numbers significantly less than that of the vehicle control (P < 0.01). Our results suggest that prophylaxis and treatment trials of R-FB should be extended to humans.
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PMID:R-flurbiprofen chemoprevention and treatment of intestinal adenomas in the APC(Min)/+ mouse model: implications for prophylaxis and treatment of colon cancer. 933 Oct 93


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