Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

l-Arginine is metabolized either to polyamines through arginase and ornithine decarboxylase (ODC) activities or to citrulline and nitric oxide (NO, nitrogen monoxide) through the NO synthase (NOS) pathway. Polyamine levels and ODC activity are high in tumor cells. The aim of this study was to test whether N(G)-nitro-l-arginine methyl ester (l-NAME), an inhibitor of NOS, modulates colon carcinogenesis. Adult male Wistar rats were treated with azoxymethane (AOM, 15 mg/kg ip), a chemical carcinogen, once a week for 2 weeks. One week after the second injection the rats were randomly divided into two groups. One group (n = 8) received l-NAME (10 mg/kg body wt/day) in drinking water. The control group (n = 8) received tap water. After 5 weeks, the rats receiving l-NAME showed enhanced mean basal arterial blood pressure, decreased heart rate, and a significant decrease of the cGMP content in the colonic mucosa. In both groups, AOM induced the formation of colonic aberrant crypt foci (ACF). In l-NAME-treated rats, the number of ACF was higher than in controls by 47%. ODC activity was enhanced by 11-fold. S-Adenosyl-methionine-decarboxylase activity and putrescine concentration were significantly increased in the colonic mucosa of l-NAME-treated rats. The data suggest that l-NAME promotes carcinogen-induced preneoplastic changes in the colon by inhibiting NOS activity and by stimulating polyamine biosynthesis.
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PMID:Nitric oxide synthase inhibition promotes carcinogen-induced preneoplastic changes in the colon of rats. 1113 66

Saliva is an important factor in the oral cavity and could be significant in protecting against carcinogens. In experimental models of carcinogenesis, saliva was shown to have a temporary protective effect against the carcinogens DMBA and 4-nitroquinoline-oxide (4NQO). Silver-stained nucleolar organizer regions (AgNORs) are considered markers for both proliferative capacity and prognosis. The purpose of the present study was to investigate the effect of desalivation on AgNOR parameters in lesions induced by the carcinogen 4NQO in a rat model, in order to trace early nuclear changes. The study group consisted of 120 male Wistar-derived rats. The experimental group (n=56) underwent surgical desalivation; the control group (n=56) underwent a sham operation, and both groups were administered a solution of 0.001% 4NQO in the drinking water. A normal group (n=8) did not receive surgery and drank tap water. Rats were sacrificed at 7, 14, 22, and 28 weeks. Formalin fixed, paraffin embedded sections of the tongue were silver-stained and AgNOR parameters were analyzed using computerized image analysis. In both desalivated and control groups, the nuclear area was significantly higher than the normal. This difference was already evident at 7 weeks. The mean AgNOR area was significantly higher in the desalivated group at week 7 and continued to increase over time. The mean AgNOR number was also significantly higher in the desalivated group at week 7. Differences between the desalivated and control groups diminished with time. These changes in proliferative activity, as expressed by AgNOR parameters, presented earlier changes in comparison to those observed in microscopic examination of the same slides. Results suggest that saliva in the oral cavity can delay malignanttransformation, but continued exposure to the carcinogen overrides this effect. AgNOR stain seems to be sensitive and allows for early identification of intranuclear changes.
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PMID:The effect of desalivation on 4-nitroquinoline-1-oxide-induced tongue carcinogenesis: a morphometric study of nucleolar organizer regions. 1114 Sep

Chemopreventive effects were analysed of antioestrogen TAM and of MEL on NMU- or DMBA-induced mammary gland cancer, respectively, in female Sprague-Dawley rats. NMU was administered intraperitoneally in two doses each of 50 mg/kg b.w. between 46th-57th postnatal days. DMBA was given by gavage in one dose (20 mg per animal) between 50th-54th postnatal days. The treatment with MEL began 12 days and the treatment with TAM 10 days before carcinogen administration; both chemopreventive substances were administered until the end of the experiment (24 weeks after carcinogen application). TAM was administered subcutaneously twice a week in a dose 2.5 mg/kg b.w. MEL was given in tap water (20 mg/ml) daily between 3 p.m. to 8 a. m. The tumour incidence, tumour frequency per group and animal, latency period, tumour volume, body weight gain in the rats and weight of uterus (in the experiment with NMU) were evaluated. TAM suppressed carcinogenesis to 0% incidence like TAM+MEL in both the NMU and DMBA models. In NMU-induced mammary carcinogenesis MEL lowered the tumour volume (although statistically non-significantly) by 30% in comparison with the control group; in DMBA-induced mammary carcinogenesis it lowered the tumour volume (2.70 +/- 0.81 cm3 vs. 0.90 +/- 0.33 cm3) and lengthened (non-significantly) the latency period (by 12 days). The weight gain of animals in both NMU and DMBA models and relative uterus weight in the NMU model were significantly lower in the groups treated with TAM and TAM+MEL as compared to the control group and the group treated with MEL. Evaluation of the combined effect of TAM+MEL was not possible due to total suppression of carcinogenesis by TAM. TAM and TAM+MEL are highly effective agents in rat mammary carcinogenesis prevention, but the side effects of TAM in humans limits its use in clinical oncology.
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PMID:Effects of tamoxifen and melatonin on mammary gland cancer induced by N-methyl-N-nitrosourea and by 7,12-dimethylbenz(a)anthracene, respectively, in female Sprague-Dawley rats. 1123 69

The aim of the experiment was to analyse the oncostatic effect of nonsteroidal antiinflammatory drug INDO, hormone MEL and combination of both substances in DMBA-induced mammary carcinogenesis in female SD rats. Chemoprevention started 10 days before the application of the first dose of DMBA to 35-day-old rats. INDO was administered in tap water (20 microg/ml of water) for 3 days in a week (days 2, 4 and 6), MEL solution in the concentration of 20 microg/ml of tap water was administered between 3 p.m. and 8 a.m. for 4 days in a week (days 1, 3, 5 and 7); during other days the animals drank tap water only. In combined chemoprevention, rats were drinking solutions of INDO and MEL according to the above-mentioned scheme. DMBA in the dose of 10 mg/rat was administered intragastrically using a probe to all rats 3 times on postnatal days 45, 50 and 55. There were four experimental groups: group 1--without chemoprevention, group 2--INDO treatment, group 3 --MEL treatment, group 4--application of INDO + MEL. The experiment lasted 26 weeks from the first administration of DMBA, when the final incidence and frequency of tumours per animal and group, as well as latency and average volume of tumours were evaluated. The content/concentration of malondialdehyde (MDA) was determined in selected tissues as a criterion of lipoperoxidation, considering its potential influencing by chemoprevention. The tumour incidence in controls was 100%; INDO reduced the incidence (36.84%) and frequency per group and animal, decreased the mean volume of tumours and prolonged the latency. Chemoprevention using combination of INDO with MEL was successful like that with INDO; however, it did not influence the tumour volume. MEL decreased the incidence to 42.11% and pronouncedly reduced the tumour frequency per group. INDO, administered alone or in combination with MEL, reduced an increased content/concentration of MDA in the liver, bone marrow and serum of tumour-bearing rats. INDO, MEL and INDO + MEL had a pronounced chemopreventive effect and showed to be a favourable combination in prevention of experimental mammary carcinogenesis.
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PMID:Preventive effect of indomethacin and melatonin on 7, 12-dimethybenz/a/anthracene-induced mammary carcinogenesis in female Sprague-Dawley rats. A preliminary report. 1132 Dec 52

We determined the effects of a crude green tea extract given as drinking fluid on the promotion/progression phase of colon carcinogenesis in rats after induction of the neoplastic process by azoxymethane. Adult Wistar rats were given azoxymethane (15 mg/kg i.p.) once a week for two weeks. One week after the second injection, the rats were randomly divided into two groups. One group (n = 8) received daily prepared aqueous solutions of green tea extracts (GTE; 0.02%, wt/vol); the control group (n = 8) received tap water. After six weeks, rats receiving GTE showed a 60% reduction in the number of colonic preneoplastic lesions (aberrant crypts). The number of individual crypts per aberrant crypt focus (crypt multiplicity) was significantly reduced in the GTE group; the majority (80%) of the remaining aberrant foci contained only one or two preneoplastic crypts. A significant and selective decrease of cyclooxygenase (COX)-2 activity was observed in the colon of rats receiving GTE (23 +/- 3 vs. 117 +/- 30 mU/mg protein in controls), whereas COX-1 showed no alterations. Our data demonstrate that GTE reduces COX-2 and suppresses the formation of colonic preneoplastic lesions. They provide new insights into the mechanism of chemopreventive and anti-inflammatory properties of green tea.
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PMID:Suppression of azoxymethane-induced preneoplastic lesions and inhibition of cyclooxygenase-2 activity in the colonic mucosa of rats drinking a crude green tea extract. 1134 Oct 46

The effects of combined administration of a reactive oxidant, monochloramine, and a mucoregulatory agent, ambroxol, on the development of gastric cancers induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) were investigated in inbred Wistar rats. After receiving oral MNNG and regular chow pellets for 25 weeks, rats received regular chow pellets or chow pellets containing 20% ammonium acetate, and normal tap water or water containing 30 mM sodium hypochlorite, with or without subcutaneous injection of ambroxol at high or low doses, until the end of the experiment at week 52. Treatment with both ammonium acetate and sodium hypochlorite, which produce monochloramine, significantly increased the incidence of gastric cancers at week 52, whereas concomitant administration of ambroxol with ammonium acetate and sodium hypochlorite significantly attenuated this enhanced gastric carcinogenesis. Results also revealed that ambroxol scavenged monochloramine. Because monochloramine is closely related to Helicobacter pylori-associated gastric carcinogenesis, these findings suggest that ambroxol may prevent H. pylori-associated gastric carcinogenesis.
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PMID:Attenuation by ambroxol of monochloramine-enhanced gastric carcinogenesis: a possible prevention against Helicobacter pylori-associated gastric carcinogenesis. 1140 15

The change of the toxicity of chlorinated water after chlorine injection was examined. For the measurement of toxicity, chromosomal aberration test and transforming test were carried out as indexes to initiating activity and to promoting activity in the carcinogenesis process, respectively. Activity inducing chromosomal aberrations of chlorinated humic acid gradually decreased with time after chlorination. In contrast, activity inducing transformations measured by the two-stage assay gradually increased. Thus, the toxicity that decreases or increases is present in chlorinated water. Furthermore, activity inducing transformations measured by the non-two-stage assay gradually decreased. This direction of change was reverse to that of activity inducing transformations by the two-stage assay and consistent with that of activity inducing chromosomal aberrations. It is speculated that the main reason of decreasing activity inducing transformations by the non-two-stage assay is because initiating activity detected as activity inducing chromosomal aberrations in chlorinated water decreases drastically. Directions of changes of total organic halogen and carbonyl group were qualitatively consistent with that of activity inducing chromosomal aberrations. Directions of changes of chloroform and dichloroacetic acid were qualitatively consistent with that of activity inducing transformations by the two-stage assay. Findings of this study suggest that further research is necessary to compare carcinogenicity of tap water near water purification plant and distant tap water.
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PMID:Changes of activity inducing chromosomal aberrations and transformations of chlorinated humic acid. 1145 60

The present study was designed to investigate the effects of fermented miso in the diet on the induction of gastric tumors by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in male CD (SD) rats. A total of 120 animals, 6 weeks of age, were divided into 6 groups and given MNNG (100 ppm) in the drinking water for 16 weeks. Starting 1 week before the carcinogen treatment the rats were fed a normal control MF solid diet, or the same diet containing 10% long-term fermented, medium- or short-term fermented miso, or 1% NaCl until the end of the MNNG exposure period. They were then maintained on the MF control diet and normal tap water until the autopsy time point at 52 weeks. The long-term fermented miso significantly reduced the size of the gastric tumors as compared with the other groups. The present results thus indicate that dietary supplementation with long-term fermented miso could act as a chemopreventive agent for gastric carcinogenesis.
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PMID:Inhibition by long-term fermented miso of induction of gastric tumors by N-methyl-N'-nitro-N-nitrosoguanidine in CD (SD) rats. 1195 37

Differences in the modifying effects of green tea catechins (GTC) on intestinal carcinogenesis by different formulations, doses and administration routes were investigated in male rats pretreated with 1,2-dimethylhydrazine (DMH). One hundred and eighty nine F344 male rats received subcutaneous injections of DMH at 40 mg/kg body weight twice a week for 3 weeks. Three days after completion of the carcinogen treatment, they were divided into nine groups. Each was administered a different source of 0.1% or 0.01% of GTC (Mitsui Norin Co. (M) or Taiyo Kagaku Co. (T)) either in the diet (D) or the drinking water (W), or basal diet and tap water alone without GTC for 33 weeks and then killed for autopsy. The survival rate tended to be lower with 0.01% MGTC (W) group than in the other groups. In the large intestine, although the multiplicity and/or incidences of adenomas showed tendencies for dose-dependent decrease in all GTC groups, and the average volumes of tumors tended to be decrease dose-dependently in the MGTC (W) and TGTC (W) groups, the multiplicity of carcinomas did not show such a trend, rather being significantly increased in the 0.01% MGTC (D) and 0.1% TGTC (W) groups. In the small intestine, the incidence and the multiplicity of tumors in all GTC treated groups had a tendency to decrease. On the other hand, the volume of tumors was increased with statistical significance in the 0.01% MGTC (W) and 0.1% TGTC (W) groups. Thus it can be concluded that GTC does not exert chemopreventive effects on intestinal carcinogenesis irrespective of its formulation, dose or route of administration.
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PMID:Lack of inhibitory effects of green tea catechins in 1,2-dimetylhydrazine-induced rat intestinal carcinogenesis model: comparison of the different formulations, administration routes and doses. 1240 61

The effect of various regimens of treatment with melatonin on the development of mammary tumors in HER2/neu transgenic mice was investigated. Female HER-2/neu mice starting from the age of 2 months were kept under standard light/dark regimen and as given melatonin with tap water (20 mg/l) during the night time 5 times monthly (interrupted treatments) or constantly to natural death. Intact mice served as controls. Treatment with melatonin slowed down age-related disturbances in estrous function most in the group exposed to interrupted treatment with the hormone. Constant treatment with melatonin decreased incidence and size of mammary adenocarcinomas, and incidence of lung metastases, compared to controls. The number of mice bearing 4 and more tumors was reduced in the group with constant melatonin treatment. Interrupted treatment with melatonin promote mammary carcinogenesis in HER-2/neu transgenic mice. The data demonstrate the regimen-dependent inhibitory effect of melatonin on the development of spontaneous mammary tumors in HER-2/neu mice but not on overall survival with implication about the likely cause of the effect. Polycystic kidney disease is common in this transgenic line. Adverse effect of melatonin on the life span in our study may be unique to the transgenic model used and may not be relevant to the suppressive effect of melatonin in delay of mammary cancer.
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PMID:The effect of melatonin treatment regimen on mammary adenocarcinoma development in HER-2/neu transgenic mice. 1247 12


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