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

A method was devised to quantitate N-acetoxy-N-acetyl-2-aminofluorene (N-AcO-AAF) induced crosslinking of the ionic complex between [methyl-3H]thymidine labeled pBR322 DNA and lysozyme. This involved chromatography of the modified complex on Sephadex CM 25 with a high salt buffer that dissociated the non-covalently bound complex and permitted early elution of unbound [3H]DNA. The crosslinked complex was then eluted with buffer at pH 10.5. The amount of crosslinking was a function of the carcinogen concentration in the reaction mixture containing the complex. Addition of the spin trap nitrosobenzene or the radical trap 2,2-diphenyl-1-picrylhydrazyl to the complex prior to the addition of N-AcO-AAF decreased crosslinking. Reaction of the carcinogen with a solution of [methyl-3H]thymidine labeled Escherichia coli DNA led to the formation of tritiated water that was azeotropically distilled from the mixture. If nitrosobenzene was added prior to the carcinogen, the amount of tritium water released was depressed. Addition of N-AcO-AAF to a mixture of acrylamide and bisacrylamide increased its relative viscosity. Far u.v. irradiation of the complex or reacting it with ammonium persulfate that dissociates to the sulfate anion radical, SO(4), induced crosslinking. While these observations support a free radical mechanism for crosslinking, whether the free radicals arise from heterolytic or homolytic cleavage of N-AcO-AAF remains undetermined.
Carcinogenesis 1983
PMID:Evidence that N-acetoxy-N-acetyl-2-aminofluorene crosslinks DNA to protein by a free radical mechanism. 634 30

The Committee on Diet, Nutrition, and Cancer of the National Academy of Sciences recently evaluated the role of diet in carcinogenesis. Both epidemiological and laboratory evidence suggests that a high intake of total fat increases susceptibility to cancer of different sites, particularly the breast and colon. In epidemiological studies frequent consumption of certain fruits and vegetables and in laboratory experiments some components of fruits and vegetables, especially cruciferous vegetables, appear to decrease the incidence of cancers at various sites. In contrast, frequent consumption of salt-cured, salt-pickled, or smoked foods, possibly because they may contain nitrosamines or polycyclic aromatic hydrocarbons, appears to increase the risk of esophageal or stomach cancer. Excessive alcohol consumption among smokers appears to be associated with an elevated risk of cancers of the oral cavity, esophagus, larynx, and respiratory tract. Interim dietary guidelines to reduce the risk of cancer were proposed in accordance with these conclusions. No definitive conclusions were reached for other dietary factors, including total calories, cholesterol, fiber, and selenium, nor could the quantitative contribution of diet to overall cancer risk be estimated.
 ...
PMID:Diet, nutrition, and cancer: interim dietary guidelines. 657 85

The carcinogenic or cocarcinogenic effects of bile or bile acid on stomach carcinogenesis were investigated in inbred W rats. Bile or bile acid was introduced into the stomach by choledochogastrostomy or with food after the administration of N-methyl-N'-nitro-N-nitrosoguanidine [(MNNG) CAS: 70-25-7; 1-methyl-3-nitro-1-nitrosoguanidine] in drinking water. The animals that received MNNG and bile or sodium taurocholate (CAS: 145-42-6; N-choloyltaurine sodium salt) had a significantly higher incidence of hyperplastic and neoplastic lesions in the stomach mucosa than did the relevant MNNG-treated controls. The result suggested an enhancing effect of bile and sodium taurocholate in stomach tumorigenesis.
 ...
PMID:Enhancing effect of bile and bile acid on stomach tumorigenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine in Wistar rats. 659 82

A promoting effect of large bowel contents on colonic carcinogenesis as seen in the animal model is still incompletely explored in man. We investigated simultaneously deoxycholate absorption (as marker of colonic mucosal exposure to tumour promoting bile salt metabolites), mouth-anus transit time, and the ratio of anaerobic to aerobic bacteria in stool in 10 persons with colonic adenomas and in 10 age matched control subjects. We found that anaerobic/aerobic ratios and colonic deoxycholate absorption were higher in patients with colonic adenomas (p less than 0.002 and p less than 0.001) and that these parameters were clearly interrelated, which also applied to intestinal transit times and the anaerobic/aerobic ratios. These data are consistent with a promoting effect of the intracolonic environment on development of adenomas in man. Long term induction of a more aerobic colon flora and shortening of intestinal transit time may diminish bile-salt induced tumour promotion in adenoma patients.
 ...
PMID:Intracolonic environment and the presence of colonic adenomas in man. 661 67

Because the composition of faeces modulates colorectal carcinogenesis, promotional effects of the secondary bile salt sodium deoxycholate (SDC) were compared with those of dilute homogenised faeces (12.5% w/v) or saline alone in rat colon isolated from the faecal stream as a Thiry-Vella fistula (TVF). Each fluid was used to irrigate a group of TVFs 3 times per week for 12 weeks. Other rats had TVF without irrigation or colonic transection and reanastomosis (sham TVF). Operations followed a 6-week course of azoxymethane injections. At sacrifice 15 weeks postoperatively crypt depth and tumour yield were reduced to the same extent in both the non-irrigated TVFs and the SDC-irrigated TVFs, when compared to shams. Irrigation with faeces and saline completely restored crypt depth and partly restored tumour yields to the levels in shams. Tumours were smaller in the SDC group than in the other 4 groups. While tumours developed mainly in the left colon of shams, there was significantly more even distribution in the TVFs. Exclusion of the colon from the faecal stream leads to mucosal hypoplasia and impaired carcinogenesis. Irrigation with faeces or saline partly reverses these changes. Deoxycholate has no such effect and clearly is not co-carcinogenic in this model.
 ...
PMID:Adaptation and carcinogenesis in defunctioned rat colon: divergent effects of faeces and bile acids. 662 49

Biphenyl and its derivatives, 2-aminobiphenyl, 2-nitrobiphenyl, 4-aminobiphenyl, 4-nitrobiphenyl, p-phenylphenol, o-phenylphenol (OPP), and o-phenylphenol sodium salt tetrahydrate (OPP-Na) were examined for their bladder carcinogenicity in rats by a short-term assay for agglutinability of bladder epithelial cells with concanavalin A. Increased agglutinability was observed after 1-week treatment with 2.0% and 1.0% OPP, 2.0% and 1.0% OPP-Na, 0.5 and 0.1% 4-aminobiphenyl, and 0.5% 4-nitrobiphenyl in the diet, suggesting carcinogenicity of these compounds in the bladder. Such an increase in agglutinability was not observed in rats fed diets containing biphenyl, 2-aminobiphenyl, 2-nitrobiphenyl or p-phenylphenol at 2.0%. With OPP-Na, an in vivo carcinogenesis experiment was performed. Bladder carcinomas developed in 14 of 36 male Fisher rats fed a 2% OPP-Na diet for 50 weeks.
 ...
PMID:Increased agglutinability of bladder epithelial cells by concanavalin A in rats fed several biphenyl derivatives. 665 51

The incorporation of tritiated deoxythymidine ([3H]dThd) into colonic DNA of male Sprague-Dawley rats treated intrarectally (i.r.) with bile salts and other substances has been investigated. Instillation of sodium deoxycholate caused an increase in the incorporation of [3H]dThd which was maximal 12 h after treatment. The level of incorporation showed a steep linear dose response from 0.5 mM to 15 mM bile salt. Higher concentrations of deoxycholate up to 300 mM only slightly increased the extent of incorporation when compared to the lower concentration. Several other substances also increased the extent of [3H]dThd incorporation; these include: chenodeoxycholate, lithocholate, sodium dodecyl sulfate, dioctyl sulfosuccinate, corn oil, beef fat, and trioctanoin. Substances which had no effect on [3H]dThd incorporation include cholesterol, dehydrocholate, sodium acetate, dextrose, and mineral oil. Many of the agents which increase colonic [3H]dThd incorporation are also known to enhance colonic tumorigenesis. These findings indicate similarities between the short-term effects, in their respective target tissues, of colon tumor promoters, and classical mouse skin tumor promoters.
Carcinogenesis 1983
PMID:Stimulation of deoxythymidine incorporation in the colon of rats treated intrarectally with bile acids and fats. 682 9

Smoke condensates obtained by pyrolysis of the cells of microorganisms isolated from food and cigarettes and of laboratory cultures were shown to be mutagenic to Salmonella typhimurium TA98 and TA100 in incorporation with liver microsomal fraction S-9 mix. The smoke condensates from salt-tolerant bacteria, which belonged to Micrococcus, Bacillus and Corynebacterium spp., showed higher mutagenic activity than those from other less salt-tolerant organisms, fish flesh or pork. Smoke deriving from microorganisms, especially salt-tolerant ones, in food or cigarettes as well as from food components might take part in human carcinogenesis because of the correlation between mutagenicity and carcinogenicity.
 ...
PMID:Mutagenicity of pyrolysates of salt-tolerant bacteria from food and cigarettes. 683 95

The ability of cytosolic 3-methylcholanthrene binding proteins from rat liver to interact with DNA was studied using DNA-cellulose chromatography. Two DNA binding fractions, eluting in 0.15 M KCl (peak 1) and 0.33 M KCl (peak 2), were observed on salt elution from a denatured DNA-cellulose column which had been incubated with rat liver cytosol containing radiolabelled 3-methylcholanthrene. No detectable DNA binding fractions were found when columns containing cellulose alone or native DNA-cellulose were used. Temperature activation of the cytosolic proteins containing 3-methylcholanthrene did not result in a significant difference in DNA binding characteristics when compared with a non-treated sample. The pretreatment of rats with Aroclor 1254 induced peak 1 3.7 fold over control values. An analysis of the proteins present in peaks 1 and 2 from control and induced rats was carried out using sodium dodecyl sulfate polyacrylamide gel electrophoresis. Comparative DNA-cellulose chromatography of cytosolic liver proteins from a cytochrome P-448 inducible mouse strain (DBA/6J) and non-inducible mouse strain (DBA/2J) showed much higher levels of DNA binding by protein bound 3-methylcholanthrene from C57BL/6J hepatic cytosol.
Carcinogenesis 1980 Jun
PMID:Interaction of DNA with cytosolic 3-methylcholanthrene binding proteins from either rat or mouse liver. 727 80

The theory that bile salts may be colon tumour promoters was tested in the dimethylhydrazine (DMH)-induced rat colon cancer model. Fifty Wistar rats were randomly allocated to one of five experimental group (n = 10), all fed the same standard diet. One group served as saline-injected controls, while the other four groups received DMH (20 mg/kg body weight/rat/week s.c.) for 20 weeks. In addition, each of the DMH-injected groups concurrently received 20 weekly i.g. instillations of one of the following: cholic acid (a bile acid); cholestyramine or aluminium hydroxide (both bile acid binding agents), or water. After a years observation period, all the controls were alive and tumour-free, while all the DMH-injected rats had died of histologically proven colon cancer. Irrespective of the type of gastric instillate, there were no significant differences between the groups in terms of time to tumour presentation, survival, in the necropsy incidence of primary or metastatic colon cancer, or in the numbers of colon tumours per group. The data suggest that bile salts and bile salt binding agents are not colon tumour promoters in the rat. The bile salt theory of colon carcinogenesis may need reappraisal.
Carcinogenesis 1981
PMID:The effects of cholic acid and bile salt binding agents on 1,2-dimethylhydrazine-induced colon carcinogenesis in the rat. 727 24


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>