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Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The M1 antigens, associated with gastric fucomucin, the early oncofetal precancerous marker for the distal colon, were studied using the immunoperoxidase method in the distal colon. We compared human tumoral mucosa with that of rats during DMH-induced carcinogenesis. In both cases we examined histologically normal mucosa, mucinous hyperplasia, glands with serrated epithelium and hypermature goblet cells like those observed in human hyperplastic polyps, dysplasia, and transitional mucosa. We were able to assess similarities between these rat and human mucosae in terms of the tissue and cell location of these M1 antigens as well as the frequency of occurrence in the different comparative lesions. Thus, we demonstrated that such similarities can be observed not only at a histologic level, but also on a molecular level. The presence of M1 antigens in the human distal colon is comparable to mucous modifications induced by a chemical carcinogen, as observed during DMH-induced carcinogenesis in the rat.
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PMID:Early precancerous modifications in the mucus of human and rat distal colon: a comparative immunohistologic study. 658 80

Normal and DMH-treated male rats aged 18-20 weeks underwent surgical transection and anastomosis of the transverse colon. Animals were subsequently killed at intervals of 14, 30 and 72 days. Three hours prior to sacrifice animals were injected with vinblastine sulphate and mitotic indices were subsequently estimated in histological sections. Possible differences between experimental and control groups were tested using a Student's t-test. The results show that the accumulated mitotic indices in normal and DMH-treated colon are statistically similar. The results also show that transection and anastomosis stimulates cell division in both normal and DMH-treated colon and that the increase is of greater amplitude and more prolonged duration in the DMH-treated rats. Carcinomas developed close to the line of anastomosis in DMH-treated but not in control rats. The results support the hypothesis that non-specific injury to hyperplastic colonic epithelium promotes carcinogenesis.
Carcinogenesis 1983 Oct
PMID:The influence of surgical transection and anastomosis on the rate of cell proliferation in the colonic epithelium of normal and DMH-treated rats. 661 61

The effect of Konjac mannan (KM) on 1,2-dimethylhydrazine (DMH-induced intestinal carcinogenesis was studied in male F344 rats. Rats were fed a diet containing 5% KM at 5 weeks of age. At 6 weeks of age, all animals were given a weekly intraperitoneal injection of 20 mg DMH/kg body wt for 13 weeks and autopsied 13 weeks after the last injection of DMH. The weight gain was lower in rats fed the KM diet than in rats fed the control diet throughout the experiment (P less than 0.05). The incidence of DMH-induced colon tumors was lower in animals fed the KM diet compared to animals fed the control diet (P less than 0.05). The number of colon adenocarcinoma per animal was also lower in animals fed the KM than in animals fed the control diet (P less than 0.05). However, the incidence of tumors of the small intestine did not significantly differ between the groups fed the KM and control diets. The present study demonstrated that colon tumorigenesis induced by DMH in F344 rat was inhibited by maintaining the KM diet.
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PMID:Effect of Konjac mannan on 1,2-dimethylhydrazine-induced intestinal carcinogenesis in Fischer 344 rats. 685 May 66

Selenium in its organic and inorganic forms has been shown to inhibit the development of chemically induced, spontaneous and transplanted tumors. The present investigation was performed to study the effect of selenium (4 micrograms per ml of drinking water) on tumorigenesis of adenovirus-type-9-induced breast fibroadenomas and on 1,2-dimethylhydrazine-induced bowel carcinogenesis in WF rats. It was found that identical treatment with Se under identical conditions and with no obvious toxic effects on the rats (1) resulted in inhibition of DMH-induced large-bowel carcinogenesis; (2) facilitated induction of small-bowel cancer by the same carcinogen in the same animals, and (3) greatly facilitated induction of breast fibroadenoma by adenovirus type 9 in the same strain of rats. The effect of Se treatment on DMH-induced large-bowel carcinogenesis confirms previous findings and proves that the opposite effect on fibroadenoma development is not due to differences in e.g. effective dose, animal strains or condition of the animals. It is not yet clear through which mechanisms Se exerts these effects.
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PMID:Effect of selenium on the induction of breast fibroadenomas by adenovirus type 9 and 1,2-dimethylhydrazine-induced bowel carcinogenesis in rats. 710 71

A dose response study in carcinogenesis by 1,2-dimethylhydrazine dihydrochloride (1,2-DMH) in Swiss mice was performed. The compound was administered continuously in drinking water for life from 6 weeks of age at dose levels of 0.002, 0.001, 0.0005, 0.00025, 0.000125, 0.0000625, 0.00003125 and 0.000015625%. A positive correlation was established between the dose levels of 1,2-DMH and the yield of blood vessel tumors. In addition, the latency periods for these tumors diminished when the dose levels of the carcinogen decreased. Although some of the treatments induced lung tumors, no association was observed between the dose levels of the carcinogen and the lung tumor incidence. The study thus provides an example in which the continuous lifespan administration of a carcinogen resulted in a partial dose response effect. This method of administration closely resembles some of the human exposure situation.
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PMID:A carcinogenicity dose response study by continuous administration of 1,2-dimethylhydrazine dihydrochloride in mice. 716 54

Enhanced lipid peroxidation potential was measured in Holtzman rat colon tumors induced by chronic subcutaneous injection of 1,2-dimethyl-hydrazine as compared with normal colonic tissue. The peroxidation potentials were determined in the mitochondrial cellular components by measuring the ferrous-ascorbate induced formation of malondialdehyde. The tumor mitochondria were found to peroxidize at a rate 8-10-fold higher than the comparable normal tissue components. In addition, we found that the mitochondria from the cancer cells exhibited reduced NADH-cytochrome c reductase activity. These observations suggest an involvement of non-enzymatic free radical flux in DMH-induced carcinogenesis, which may be the result of structurally altered mitochondrial membranes.
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PMID:Evidence for a defective mitochondrial membrane in 1,2-dimethylhydrazine-induced colon adenocarcinoma in rat: enhanced lipid peroxidation potential in vitro. 722 56

We studied DMH induced colon cancer in 120 wistar rats, which were divided into 8 groups based on different diets. They were killed and autopsied on 4 weeks after the last injection of DMH. The tumors in various organs including its characteristics, number, site, histological types and ultrastructural changes were observed. The results showed that high fat diet has a significant effect on DMH induced colon cancer. Selenium and calcium can inhibit the effect of DMH and decrease the incidence of colon cancer. Selenium can also interfere the effect of high fat diet but germanium has no effect on colon carcinogenesis.
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PMID:[Interference of selenium germanium and calcium in carcinogenesis of colon cancer]. 755 87

Effects of dietary supplementation with the antioxidants ellagic acid, quercetin and vanillin were examined using a medium term multi-organ carcinogenesis model in rats. Groups of 10-15 male F344 rats were given i.p. injections of diethylnitrosamine (DEN, 100 mg/kg body wt.) and N-methylnitrosourea (MNU, 20 mg/kg body wt), s.c. injections of 1,2-dimethylhydrazine (DMH, 40 mg/kg body wt.), together with 0.05% N-butyl-N-(4- hydroxybutyl)nitrosamine (BBN) and 0.1% 2,2'-dihydroxy-di-n-propylnitrosamine (DHPN), both in the drinking water, for a total multiple initiation period of 4 weeks (DMBDD) treatment). Ellagic acid, quercetin or vanillin, each at a dose of 1% each in the diet were administered from 1 day before and throughout the carcinogen exposure period, or after completion of the initiation regimen. All surviving animals were sacrificed at the end of week 36, and major organs were examined histopathologically. In the small intestine, significant reductions in the incidence and number of tumors (adenomas and carcinomas) were observed in the groups administered ellagic acid during (8%, 0.08 +/- 0.29) or after (8%, 0.08 +/- 0.29) DMBDD treatment, and those receiving quercetin after DMBDD treatment (0%) compared to the control value (57%, 1.07 +/- 1.21). Although the incidences were not statistically significant, slightly decreased numbers of small intestinal tumors were found in the groups receiving vanillin during (0.33 +/- 0.72), or after (0.40 +/- 0.83) DMBDD treatment. The incidence of large intestinal carcinomas in the group treated with vanillin during DMBDD treatment was significantly higher (73%) than the control value (21%). These results indicated that while ellagic acid and quercetin exerted potent chemopreventive action in both the initiation and promotion stages in the present experimental system, their beneficial effects were restricted to the small intestine. Since small intestinal carcinomas are very infrequent in humans, the advantages of these phenolic compounds for human application as chemopreventors should not be overestimated.
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PMID:Modulating effects of ellagic acid, vanillin and quercetin in a rat medium term multi-organ carcinogenesis model. 762 39

The measurement of 7-methylguanine (7-meG) in white blood cells (WBC) is a promising biomarker of individual human exposure to environmental methylating agents. To test the validity of using WBC as a surrogate dosimeter for internal tissues, levels of 7-meG were measured in rat WBC, liver and target organs for carcinogenesis 16 h after oral administration of several methylating carcinogens (DMN, DMH, NNK, NMBA). 7-MeG was detected in WBC DNA but levels were far lower than in internal organs. While the ratio between 7-meG formation in target organs and WBC was highly variable depending on the carcinogen administered, the ratio between 7-meG in the liver and WBC was in the same order of magnitude for each carcinogen, ranging from 81 to 143. In addition, levels of 7-meG in the liver and WBC within individual animals were highly correlated (r = 0.94, P < 0.0001). These results confirmed our previous observations with the same carcinogens after intraperitoneal injection. In order to assess if the lower level of 7-meG in WBC was a result of a low metabolism of methylating agents in WBC, microsomes were prepared from control rat lymphocytes and DMN demethylase activity was measured. The total amount of microsomal proteins was extremely low, especially in comparison with hepatic cells, and the enzymatic activity was less than 0.48 nmol HCHO/min/mg protein, while an activity of 1.26 nmol HCHO/min/mg protein was measured in liver microsomes. Taken together, these results suggest that the presence of 7-meG in WBC DNA reflects an exposure to methylating agents; the level of 7-meG in WBC seems predictive of the level of adduct in the liver, possibly because active methylating species are formed in the liver and then transferred into the hepatic circulation, where the WBC are exposed. It is now important to examine this relationship in humans where exposures are generally to lower levels of carcinogens over long time periods.
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PMID:Effect of route of administration of environmental methylating agents on 7-methylguanine formation in white blood cells and internal organs: implications for molecular epidemiology. 781 31

Chemoprevention of liver carcinogenesis by S-adenosyl-L-methionine (SAM) was studied in F344 male rats. The rats were given 1,2-dimethylhydrazine (1,2-DMH) 2 HCl (100 mg/kg, i.p.) 18 h after two-thirds hepatectomy. One week later they were fed a semisynthetic basal diet containing 1% orotic acid (OA) for 29 weeks. At this time the rats were transferred to the basal semisynthetic diet and were killed 3 weeks later. SAM treatment (384 mumol/kg/day, i.m.), was started 1 week after 1,2-DMH and was continued up to the end of the experiment. Controls received solvent alone. SAM exerted an inhibitory effect on the induction of preneoplastic and neoplastic lesions. For example, nodules with diameters of 1-2 and 2-6 mm exhibited a decrease in both incidence and number per liver, while no such inhibitory effect was seen in the category of larger nodules. Furthermore, hepatocellular carcinoma (HCC) also exhibited a decrease in the SAM-treated group. The number/liver and incidence were 0.04 and 4.8% respectively in the SAM-treated group, compared to 0.38 and 37.8% in the control group. Microscopic examination showed the presence of well-differentiated carcinomas and atypical nodules in control rats, while only one small, well-differentiated tumor and one nodule with patterns of initial transformation were seen in SAM-treated rats. No patchy staining of glutathione-S-transferase, indicative of remodeling, was observed in nodules of both SAM-treated and control rats. Nodules and HCCs developing in SAM-treated rats exhibited a relatively high number of apoptotic bodies. Apoptotic bodies count showed 2.8- and 1.8-fold increases in nodules and HCCs of SAM-treated rats with respect to controls. These results indicate that SAM exerts a chemopreventive effect on hepatocarcinogenesis induced by the OA model. SAM seems to be more effective in inhibiting nodule to HCC progression than on the growth of nodule per se. The inhibitory effect is associated with an increase in cell loss by apoptosis in nodules and HCC.
Carcinogenesis 1995 Feb
PMID:Chemoprevention by S-adenosyl-L-methionine of rat liver carcinogenesis initiated by 1,2-dimethylhydrazine and promoted by orotic acid. 785 77


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