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At least 19 recordsLinked to original sources
PubMed1976

Experimental investigations on the influence upon the chemical carcinogenesis. IIIrd communication: studies with 1,2-dimethylhydrazine.

After ten times monthly, subcutaneous, injections of 30 mg/kg 1,2-dimethylhydrazine (DMH) to Sprague-Dawley-rats, malignant tumors were found in approximately 90% of the animals after a mean induction period of approximately 330 days. Injections were started on the 2nd day of life and maintained during 10 months. 72% of the tumors induced were formed in the colon, 17% were squamous cell carcinomas of the ear duct, adenosarcomas of the kidney and hepatocellular carcinomas were found in 13 and 11% of the animals, respectively. Additional treatment with immunodepressive (cyclophosphamide, methotrexat, hydrocortisone) and immunostimulating substances (BCG, albumin, vitamin A-acid) as well as an enzyme-stimulating agent (Luminal) did not alter incidences and induction periods of tumors. After application of a vegetarian diet, the rate of liver and kidney tumors was diminished significantly and induction periods of intestinal and ear duct tumors increased.

Animals↗
PubMed1978

Pathological features of the colonic tumours induced in rats by the administration of 1,2-dimethylhydrazine.

The parenteral administration of 1,2-dimethylhydrazine to rats caused the development of colonic neoplasms in about 90% of animals by 24--30 weeks of treatment. Usually there were multiple tumours with a mean of 2.7 per rat. The lesions have been classified histologically into adenomata (26% of all tumours) and carcinomata, the latter showing varying degrees of differentiation. No completely anaplastic tumours were seen, and there were none originating in connective tissue. The distributions of the different tumour types along the length of the colon varied. The more benign lesions were situated predominantly in the distal half of the colon, while the poorly differentiated adenocarcinomata were concentrated in the proximal third of the colon. There was good evidence to suggest that adenomata often progressed to frank malignancy in the distal colon. In the proximal part, however, it appeared that tumours frequently developed de novo as poorly differentiated carcinomata. Perhaps regional variations in the kinetic organisation of the normal colonic mucosa somehow influence the nature of the neoplastic change induced by DMH, thus accounting for the differences in tumor distribution. After 24 weeks of DMH treatment there was only a small increase in the mean number of tumours per rat.

Adenocarcinoma↗
PubMed1979

DNA-damaging and mutagenic effects of 1,2-dimethylhydrazine on Bacillus subtilis repair-deficient mutants.

Mutagenic, DNA-damaging, and in vivo alteration of DNA have been demonstrated for 1,2-dimethylhydrazine (DMH), a potent inducer of adenocarcinomas of the large intestine and colon of rats. These activities are pH-dependent, with 6.5 giving optimum response. There was no requirement for metabolic activation with rat-liver S9 mix when the appropriate Bacillus subtilis mutant strains were used. The Rec- strains recA8 and mc-1 were greater than 300-fold more sensitive to the DNA-damaging activity of DMH than was their isogenic wild-type parent. The DNA isolated from DMH-treated mc-1 had altered spectroscopic characteristics, and gave a greatly reduced transformation efficiency. Treatment of B. subtilis strain TKJ6321 with DMH at pH 6.5 induced His+, Met+ mutations in substantial numbers at low concentrations of this chemical. The use of B. subtilis mutants in these studies has therefore made it possible to demonstrate mutagenic and DNA-damaging activity in bacteria for this potent carcinogenic chemical.

Bacillus subtilis↗
PubMed1979

The multiple forms and kinetic properties of the N-acetyl-beta-D-hexosaminidases from colonic tumours and mucosa of rats treated with 1,2-dimethylhydrazine.

The separation and purification of the N-acetyl-beta-D-hexosaminidase activities from tumours induced by 1,2-dimethylhydrazine in the rat colon and from colonic mucosa of tumour-bearing animals are reported. Mucosa contained N-acetylhexosaminidases A and B, as well as a third form whose properties with regard to electrophoretic mobility and thermostability lay between those of A and B. Tumours contained only N-acetylhexosaminidase A and B activities. Each form possessed both N-acetylglucosaminidase (EC 3.2.1.30) and N-acetylgalactosaminidase (EC 3.2.1.53) activities, which could not be separated by a variety of techniques. The alteration of the ratio of the two specific activities in each form during purification, together with differences in the kinetic inhibition constants and behaviour during inactivation by various reagents or a temperature of 50 degrees C, supported the belief that each form contains the two enzyme activities, glucosaminidase and galactosaminidase, at separate active sites. This model is in contrast with that reported for these activities from a number of other sources. A variety of treatments reported to cause the conversion of form A into a form resembling B failed to produce such an effect on the rat colonic hexosaminidases.

Animals↗
PubMed1976

Nitrogen intake and tumorigenesis in rats injected with 1,2-dimethylhydrazine.

Tumor incidence was studied in 1,2-dimethylhydrazine (DMH) injected male rats assigned at weaning to isoenergetic casein-sucorse deits containing 7.5%, 15%, or 22.5% protein with or without 2.5% urea. Twenty rats fed each diet were given weekly intraperitoneal injections of DMH (15 mg/kg body weight/week) for the first 24 weeks and 20 were given saline. Of 96 DMH-injected rats necropsied after 28 weeks, 88 were necropsied during the 32nd or final week of the experiment. Adenocarcinomas of the small and large intestine were larger and significantly more numberous in rats fed 15% and 22.5% dietary protein. Keratin producing papillomas of the sebaceous glands of the external ear were observed first at 21 weeks in DMH-injected rats fed 22.5% protein. These were subsequently observed in some rats from all DMH-treated groups. As time progressed, the ear tumors increased in size and number in all groups but the greatest incidence was in the group fed 22.5% protein. No tumors were observed in saline-injected rats. Urea feeding did not increase the number of tumors nor cause changes in pH, urease activity or ammonia concentration of contents of the colon or cecum, or blood cholesterol. As dietary protein increased, cecal ammonia concentrations rose while both colon and cecal pH dropped. Portal blood urea and cholesterol reose as dietary protein was increased. DMH-treated rats had significantly higher concentrations of colon and cecal ammonia and lower blood cholesterol. Altough the rats fed 7.5% protein gained significantly less weight during 0 to 6 weeks of feeding, their weight gain was significantly higher during 6 to 26 weeks. No tumors were found in rats necropsied at 16 weeks.

Adenocarcinoma↗
PubMed1977

Gamma glutamyl transpeptidase in colon cancer induced by 1,2-dimethylhydrazine.

The study of the gamma-glutamyl transpeptidase (GTase) in colon of adult rats showed that in the sequence: duodenum, jejunum, ileum, cecum and colon, the colon has the lowest activity. There are, on the other hand, relatively small differences between GTase activities in the ascending, transverse and descending portions of the large intestine. GTase activity in the colon of neonatal rat is several times higher than in the colon of adult rats. Colon adenocarcinoma induced by 1,2-dimethylhydrazine were found to have a much higher GTase activity than the homologous normal tissue. Because these tumors resemble human colonic adenocarcinomas, it is suggested that the assay of GTase levels of human colon mucosa might be of potential value in the diagnosis of neoplastic changes.

Adenocarcinoma↗
PubMed1977

Dependence of 1,2-dimethylhydrazine metabolism on its treatment schedule.

The content of cytochromes P-450 and b5 in rat liver microsomes, as well as the extent of labeling of nucleic acids and proteins of the liver and kidneys and of mucosa from different intestinal segments, was studied in rats injected daily or once a week subcutaneously with similar total doses of 1,2-dimethyl-hydrazine (SDMH) and in untreated rats. Daily SDMH administrations led to a decrease in cytochrome P-450 activity. Pretreatment of rats with unlabelled SDMH resulted in decreased labeling of DNA, RNA, proteins, and acid-soluble fractions after [3H]SDMH injection. A more pronounced effect was found after the daily treatment.

1,2-Dimethylhydrazine↗
PubMed1976

Distribution and carcinogenic action of 1,2-dimethylhydrazine (SDMH) in rats.

The radioactivity in the blood, bile, and contents from different parts of the gastro-intestinal tract was estimated for different time intervals up to 24 h after 3H-SDMH injection to rats. 65% of the radioactivity was excreted in the urine. Of the total quantity of radioactive products entering the intestine, 96% is brought with bile and only 4% from the circulation through the wall of the intestine. This latter small amount of SDMH metabolites plays a leading role in the genesis of intestinal tumours. This conclusion was proved by the observation that the intestinal tumours developed in different isolated segments of the gut where the entry of bile was excluded and by published data indicating that SDMH is excreted unchanged in the bile. It was shown that the carcinogenic effect depends upon the dose schedule of carcinogen treatment, probably, due to the changes in the SDMH metabolism. The optimal conditions for induction of intestinal tumours occur after administration of SDMH in a dose of 21 mg/kg body weight once a week. Hypothetic SDMH metabolic pathways leading to tumour production have been considered in the light of available experimental data.

Animals↗
PubMed1976

Production of intestinal and other tumours by 1,2-dimethylhydrazine dihydrochloride in mice. II. Scanning electron microscopic and cytochemical study of colonic neoplasms.

Thum of colon induced by repeated subcutaneous injections of 1,2-dimethyl-hydrazine dihydrochloride in mice were studied by scanning electron microscopy. In addition, the surface composition of normal and malignant colonic epithelial cells were investigated by ultrastructural cytochemistry. The neoplastic, nodular tumour masses which protruded into the lumen of colon displayed an asymmetrical, irregular growth pattern and surface contour. In contrast to the normal surface structure, the shape of crypt openings in malignant areas was distorted and they were irregularly spaced. Cells varying in size and shape in the intercrypt regions often formed random patterns of elevations and depressions. Microvilli on neoplastic cells were larger, more club-shaped and showed more disorderly arrangement than their normal counterparts. The distribution and quantity of surface acid mucopolysaccharide content and adenosine triphosphatase activity varied considerably from cell to cell in the neoplastic epithelium while they were more uniform in the normal colonic surface cells.

Adenocarcinoma↗
PubMed1977

Cholecystectomy and carcinoma of the colon. An experimental study.

The influence of cholecystectomy on the development of carcinoma of the colon is investigated. The experimental results show a significantly increased rate of carcinoma of the colon induced by subcutaneous injection of 1,2-Dimethylhydrazin (DMH) in the mouse after cholecystectomy. After 10 weekly injections of 15 mg/kg DMH, 70% of the animals with cholecystectomy developed carcinoma. Only 16% of the mice with similar treatment but without cholecystectomy had carcinoma. The cocarcinogenic effect of cholecystectomy is assumed to be due to the increased production of secondary bile salts by the colonic bacteria and the lacking of the resorptive function of the gallbladder for some carcinogenic substances passing through the liver. The background of this experimental studies are the clinical findings that 10% of patients with carcinoma of the large bowel had previous cholecystectomy.

Animals↗
PubMed1977

Experimental carcinogenesis in the resected colon of the rat.

Until now, carcinoma of the large intestine resected previously for benign disease has not been published. However an increasing number of patients resected for Crohn's disease, diverticulitis or trauma may reach nowadays a high lifespan. On the other hand, it is known that the gastroenteral anastomosis is predisposed to cancer development. In this study, the question of whether the large intestine following colotomy or ileotransversostomy is sensitive to carcinogenesis is examined. Male Wistar rats, subjected to colotomy or resection and ileotransversostomy, were treated weekly by subcutaneous injection of 1,2-dimethylhydrazine (12 mg/kg body weight) for seven weeks. The animals were killed 54 weeks after the first injection. At autopsy, 21 out of 29 operated rats had developed adenocarcinomas of the remaining colon. Intact control animals had the same incidence of malignant degeneration of the large bowel. When the anastomosis is chronically irritated by inflammation or by formation of a diverticulum, development, of carcinoma near the stoma was observed. This was the case in three rats of 28 animals. The results demonstrate that the resected colon of the rat is not more sensitive to experimental carcinogenesis than the intact one.

Adenocarcinoma↗
PubMed1978

Explant culture of rat colon: a model system for studying metabolism of chemical carcinogens.

An explant culture system has been developed for the long-term maintenance of colonic tissue from the rat. Explants of 1 cm2 in size were placed in tissue-culture dishes to which was added 2 ml of CMRL-1066 medium supplemented with glucose, hydrocortisone, beta-retinyl acetate, and either 2.5% bovine albumin or 5% fetal bovine serum. The dishes were placed in a controlled-atmosphere chamber which was gassed with 95% O2 and 5% CO2. The chamber then was placed on a rocker platform which rocked at 10 cycles per min causing the medium to flow intermittently over the epithelial surface. The explants were incubated at 30 degrees C. The viability of the tissue was measured both by incorporation of specific precursors into cellular macromolecules and by monitoring of tissue morphology with light and electron microscopy. Cultured rat colon was able to metabolize benzo[alpha]pyrene, 7,12-dimethylbenz[alpha]anthracene, aflatoxin B1, dimethylnitrosamine, 1,2-dimethylhydrazine, and methylazoxymethanol acetate into chemical species that bind to cellular DNA and protein.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1978

Failure of bran to protect against experimental colon cancer in rats.

The ability of dietary fibre to prevent colon cancer was tested in rats injected with 1,2-dimethylhydrazine (D.M.H.), a substance which induces cancer of the colon. 60 rats were fed the same formula solid diet but allocated three different amounts of dietary fibre--20 were given 4.8% w/w crude fibre, 20 were given 20% w/w bran, and 20 received no fibre. Half of the animals in each fibre group received a course of subcutaneous D.M.H. and half were given subcutaneous saline. After a year's observation, there was no significant difference in the incidence of, or mortality from, colonic carcinoma between the D.M.H.-treated groups.

Adenocarcinoma↗
PubMed1978

Effect of Salmonella enteritidis 11RX infection on two-stage skin carcinogenesis in mice.

S. enteritidis 11RX infection inhibits the growth of a number of transplantable tumours in mice. In addition, oral infection of mice with S. enteritidis 11RX inhibits colon carcinogenesis by 1,2 dimethylhydrazine. This study has examined the effect of S. enteritidis 11RX infection on two-stage skin carcinogenesis in mice using 7,12 dimethylbenz(a)anthracene (DMBA) as initiator and croton oil as promoter. No protection was observed in either LACA or (BALB/c x C57Bl/6J)F1 mice when live 11RX was repeatedly administered i.v. during promotion. When a protein antigen extract from S. enteritidis 11RX was administered i.v. to previously immunised mice during skin carcinogenesis, significant protection was observed both in terms of the number of mice with papillomas and the number of papillomas per mouse. However, the protection was weak and transient. LACA mice were much more susceptible to skin carcinogenesis by DMBA and croton oil than were (BALB/c x C57B1/6J)F1 mice. A preliminary study indicated that BALB/c, C57B1 and CBA mice were also relatively resistant to skin carcinogensis.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1979

Immunogenicity of chemically induced murine colon cancers.

The antigenicity and immunogenicity of three colorectal carcinomas induced in BALB/c mice by 1,2-dimethylhydrazine or N-methyl-N-nitrosourethan were studied. All tumors were readily transplantable. Two of these tumors metastasized when transplants reached sufficient size. All tumors were found to be immunogenic in the strain of origin, and all tumors were shown to contain unique tumor-specific transplantation antigens in cross-protection experiments. The use of these tumors as an animal model for studies of adjuvant immunotherapy and chemoimmunotherapy is suggested.

Animals↗