Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0699790 (colon cancer)
 28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The present study was undertaken to investigate certain dietary factors known to affect the development of colon cancer for their ability to modulate aberrant crypt foci (ACF). Male Wistar rats were initiated with oral doses of dimethylhydrazine dihydrochloride (DMH-2HCl, 20 mg/kg body wt) once a week for 10 or 20 weeks. Throughout the study the animals were fed 1) semisynthetic casein-based control diet, 2) control diet with 20% lard, 3) control diet with 20% lard and 20% dietary fiber, or 4) control diet where most of the carbohydrate pool was substituted with sucrose and dextrin. The composition of the different diets was designed to achieve equivalent intakes of essential nutrients. Animals were killed after 10, 20 and 31 weeks. The study showed a pronounced effect of dietary composition on the development of DMH-induced ACF. The diet high in sucrose and dextrin caused a statistically significant increase (p < or = 0.05) in the total number of ACF and number of small and medium ACF. Adding lard to the standard diet did not cause an increase in ACF, but if the dietary fiber was added to the high-fat diet, a statistically significant reduction (p < or = 0.05) in the total number of ACF and number of small and medium ACF was observed. The values of large and extra-large foci reflected the same effect of diets on ACF. The results indicate that tumors in the group fed the diet high in refined carbohydrates were more prominent and occurred with a higher incidence. However, the difference is based on few tumors and is not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Influence of different diets on development of DMH-induced aberrant crypt foci and colon tumor incidence in Wistar rats. 764 84

Mouse models may aid in the identification of genes involved in colon cancer. Our mating scheme involved mouse strains selected for maximum differences in susceptibility to DMH-induced colon tumors. Tumors were found in 40 of 122 progeny from a backcross to the resistant strain. We examined progeny animals for segregation of 177 genetic markers distributed at intervals of 5-30 cM on all mouse chromosomes. Multiple loci contribute to the phenotype, with significant linkage to a novel locus, Ccs1, between D12Mit5 and D12Mit6 on mouse Chr 12. Comparative maps suggest that the human homologue of Ccs1 is near FOS on human chromosome 14q.
 ...
PMID:Genetic analysis of colon cancer susceptibility in mice. 780 25

Inhibitory effects of OK-432 administered orally on DMH-induced colon tumors in rats were examined. As for the immunological parameter, NK activity was measured. ODC activity and nuclear DNA ploidy pattern of the tumor involved areas were evaluated and the histological examination was done in the process of the occurrence of tumors. Rats were divided into four groups as follows; control group, OK-432 group, DMH group and DMH+OH-432 group. As for the appearance of DMH induced colon tumors, the average numbers of tumors per rat in the DMH+OK-432 group were inhibited significantly compared with those in the DMH group, and the rate of cancer in situ in the DMH+OK-432 group significantly increased compared with that in the DMH group. NK activity of lymphocytes in the spleen and lymph nodes in the colon was increased after the oral administration of OK-432, but it was decreased following the peak activity, and it was lower level than that of the control group. An appropriate oral administration of OK-432 may be effective against chemically induced carcinoma of the colon.
 ...
PMID:[Inhibitory effects of OK-432 administered orally on colon carcinoma induced by DMH in rats]. 783 6

Aberrant crypt foci (ACF) consisting of one more single aberrant crypts (AC) are putative preneoplastic lesions that have been proposed as intermediate biomarkers for colon cancer. Using ACF as the end-point we have studied the effects of two different classes of colon carcinogens, 1,2-dimethylhydrazine dihydrochloride (DMH; 10 or 20 mg/kg body wt/injection) or its metabolite azoxymethane (AOM; 5 mg/kg) and 3,2'dimethyl-4- aminobiphenyl hydrochloride (DMAB; 50 mg/kg) in F344 and Lewis rats. Each carcinogen was given alone or DMH/AOM and DMAB were given in combination in either alternating or successive order in multiple doses. Each compound given alone induced ACF in both rat strains and the effect was most pronounced in the F344 rats. DMAB, not previously tested for ability to induce ACF in rats, was clearly less potent than DMH or AOM. The highest number of ACF was found distally in the colon, independent of treatment or rat strain. Surprisingly, DMAB markedly decreased the carcinogenic effect of DMH, evaluated both as numbers of ACF and AC per colon, as well as number of ACF with four or more AC, when both classes of carcinogens were given alternately. A more pronounced reduction was found in F344 rats than in Lewis rats, being 75-77% and 64-68% respectively with the highest DMH dose. The same tendency was found with successive exposure to DMAB followed by DMH or AOM. These differences in timing of exposure and the different metabolic pathways used by the two classes of carcinogens make a metabolic interaction unlikely as the reason for the antagonistic effect of DMAB on DMH or AOM. The type of standard diet used was found to influence the induction of ACF by the colon carcinogen DMH.
 ...
PMID:Unexpected antagonistic action of 3,2'-dimethyl-4-aminobiphenyl on aberrant crypt induction by 1,2-dimethylhydrazine or azoxymethane in rat colon. 860 73

Human epidemiological reports and rodent experimental research data indicate a possible chemopreventive effect of regular aspirin use for decreasing risk of colon and rectum cancer incidence and mortality. We have previously demonstrated that aspirin can significantly suppress proliferative parameters in normal rat colonic epithelium when examined 24 h following an acute or chronic course of aspirin administration. To investigate whether aspirin would effectively suppress known carcinogen-induced changes in colonic epithelium, rats were given single s.c. injections of either aspirin (50 mg/kg bw) or saline on days 1-3 and either 1,2-dimethylhydrazine (DMH; 12 mg base/kg bw) or DMH vehicle on day 4 of each week for eight consecutive weeks. Rats were sacrificed 4 days after the last aspirin dose and 3 days after the last DMH or DMH vehicle dose. Using the proliferative biomarkers of proliferating cell nuclear antigen positive cells per midaxial crypt section (SCC), crypt proliferative zone height (PZ), crypt differentiated zone height (DZ), and total crypt height (CH), it was found that aspirin does suppress DMH-induced increases in SCC, PZ and CH. The findings demonstrate that aspirin has a long term (i.e. several days) protective effect against early carcinogen-induced proliferative changes in rat colonic crypts which may help account for aspirin's chemopreventive action against colon cancer.
 ...
PMID:Aspirin suppresses 1,2-dimethylhydrazine-induced alteration of proliferative parameters in rat colonic crypts. 891 60

Male, F344 rats were fed ad libitum diets in which the fiber was either 10% wheat bran or 4% cellulose. The diets contained equivalent amounts of fiber. Other groups were fed wheat bran or cellulose-containing diets which were pair fed to the controls to provide 10, 20, or 30% energy restriction (ER). Colon cancer was induced by five weekly feedings of DMH. After 28 weeks, colon tumor incidence in the ad libitum fed groups was: cellulose 70%, wheat bran 42%. At 10, 20, or 30% ER tumor incidence was 46, 29, and 21% in rats fed cellulose and 17, 17, and 21% in those fed wheat bran, respectively. The data confirm the greater protective action of wheat bran compared to cellulose.
 ...
PMID:Interaction of fiber and energy registration in experimental colon carcinogens. 910 52

The aberrant crypt foci assay has been used extensively to study different compounds for chemopreventive action, but almost all investigations have used initiators not normally found in the diet. In the present study two food-borne initiators, 2-amino-3-methyl-imidazo[4,5-f]quinoline (IQ) and 2-amino-1-methyl-6-phenyl-imidazo[4,5-b]pyridine (PhIP) were used. To simulate the human exposure further, we chose a feeding regimen with continuous low IQ- and PhIP-doses. Throughout the study female mice were given diets with or without 0.03% IQ or 0.03% PhIP. Two additional groups were given azoxymethane (AOM) (5 mg/kg body weight) and 1,2-dimethylhydrazine dihydrochloride (DMH-2HCl) (20 mg/kg body weight), respectively, one dose a week for two weeks. Animals were killed after four and 10 weeks. After four weeks only the mice dosed with IQ and PhIP had aberrant crypt foci. A much higher number of aberrant crypt foci were found in the IQ mice (31.8 +/- 5.2) than in the PhIP mice (0.5 +/- 0.3). After 10 weeks aberrant crypt foci were found in all dosed groups. The IQ mice had significantly more (P < or = 0.001) small and total aberrant crypt foci than the other groups. AOM and DMH induced a higher percentage of medium or large sized aberrant crypt foci than PhIP or IQ. The interpretation of the aberrant crypt foci as precursor lesions for colon cancer in the PhIP and IQ mice is difficult because PhIP and IQ have not been reported to be colonic carcinogens. If cooked food mutagens such as IQ or PhIP are to be used as initiators in the aberrant crypt foci test, the use of rats may be preferable.
 ...
PMID:The ability of two cooked food mutagens to induce aberrant crypt foci in mice. 916 13

Our previous experimental data demonstrated that a new gastrin receptor antagonist (CR2945) has a chemopreventive effect on dimethylhydrazine-induced colon cancer in mice. The aim of this study is to test the effect of CR2945 on the appearance and distribution of aberrant crypt foci (ACF), proposed as early "preneoplastic" lesions in colon carcinogenesis, in the murine model. 176 CD1 male mice were randomly divided into 4 groups: group 1, sham group received 2 daily intra-peritoneal injections of saline solution; group 2 received 1 weekly intra-peritoneal injection of DMH 20 mg/kg, for 5 weeks, and 2 daily intra-peritoneal injections of equal volume of NaCl 0.9%; group 3 and 4 received the same weekly dose of DMH and 2 daily injections of CR2945 at the respective doses of 2.5 and 7.5 mg/Kg for 5 weeks. The rodents were sacrified 15, 20, 25, and 38 weeks after receiving the first injection. The number of ACF per area (ACF frequency), their multiplicity (number of crypts per focus), ACF frequency according to each colonic site were recorded. No ACF were found in the sham group. No substantial differences were observed in ACF distribution between the remaining groups. Our hypothesis is that CR2945 does not alter the final number of ACF but might induce a regression of some dysplastic ACF.
 ...
PMID:Distribution of 1,2 DMH-induced colonic aberrant crypt foci after administration of a gastrin receptor antagonist (CR2945), in the murine model. 1155 78

The protective effect of a curcumin analog [bis-1,7-(2-hydroxyphenyl)-hepta-1,6-diene-3,5-dione] was investigated on hepatic lipid peroxidation (LPO) and antioxidant status during 1,2-dimethylhydrazine-induced colon carcinogenesis in male Wistar rats. The effects were compared with that of curcumin, a known antioxidant and anticarcinogen. Colon cancer was induced by sub-cutaneous injection of DMH at a dosage of 20mg/kg body weight (15 doses, at 1-week intervals). DMH administered rats developed gross tumours in the colon. Enhanced lipid peroxidation in the liver of colon tumour bearing rats was accompanied by a significant decrease in the activities of glutathione peroxidase (GPx), glutathione S-transferase (GST), superoxide dismutase (SOD) and catalase (CAT). Intragastric administration of curcumin (80mg/kg body weight) and curcumin analog (80mg/kg body weight) to DMH-injected rats significantly reduced the number and size of tumour in the colon, lowered lipid peroxidation and enhanced the activities of GPx, GST, SOD and CAT in the liver. We speculate that the curcumin analog used in the present study exerts chemoprevention against cancer development at extrahepatic sites by modulating hepatic biotransformation enzymes and antioxidant status. The effect is comparable with that of curcumin. This shows that the hydroxyl group in the aromatic ring is responsible for the protective effect rather than the methoxy group.
 ...
PMID:Bis-1,7-(2-hydroxyphenyl)-hepta-1,6-diene-3,5-dione (a curcumin analog) ameliorates DMH-induced hepatic oxidative stress during colon carcinogenesis. 1220 19

Chemopreventive effects of orally administered Nigella sativa oil on the induction and development of 1,2-dimethylhydrazine-induced aberrant crypt foci (ACF), putative preneoplastic lesions for colon cancer, were investigated in Fischer 344 rats. Starting at 6 wk of age, 45 male rats (groups 1-3) were subcutaneously injected with DMH once a week for 3 wk. Group 1 (15 rats) served as a carcinogen control group without N. sativa administration. Group 2 or 3 (15 rats each) were given the oil in the postinitiation stage or in the initiation stage, respectively. Animals of group 4 (11 rats) were injected with 0.9% saline and received N. sativa oil from the beginning until the termination. At sacrifice, 14 wk after the start, the total numbers of ACF as well as those with at least four crypts were significantly reduced in group 2 (P < 0.01). However, treatment with N. sativa oil in the initiation stage (group 3) did not exhibit significant inhibitory effects except on foci with only one aberrant crypt. Immunohistochemical analysis of 5-bromo-2'.-deoxyuridine labeling in colonic crypts revealed the N. sativa oil to have significant antiproliferative activity in both initiation and postinitiation stages and especially in the latter. Histological examination revealed no pathological changes in the liver, kidneys, spleen, or other organs of rats treated with N. sativa. In addition, biochemical parameters of blood and urine as well as body weight gain were not affected. These findings demonstrate that the volatile oil of N. sativa has the ability to inhibit colon carcinogenesis of rats in the postinitiation stage, with no evident adverse side effects, and that the inhibition may be associated, in part, with suppression of cell proliferation in the colonic mucosa.
 ...
PMID:Chemopreventive potential of volatile oil from black cumin (Nigella sativa L.) seeds against rat colon carcinogenesis. 1288 Oct 14


<< Previous 1 2 3 4 5 6 Next >>