Die Vorstufen des 1,2-Dimethylhydrazin-induzierten Dick- und D�nndarmcarcinoms der Ratte

Summary.-The evolution and structure of adenomatous polyps and adenocarcinomata of the colon in NMRI mice induced by dimethylhydrazine are described. Severe toxic reactions in the liver and other organs are produced by dimethylhydrazine (DMH), but tumours are induced only in the colon and around the anus.The 100%o incidence and growth characteristics of the tumours make it potentially a good model system, but investigators should take into account the widespread nonspecific cellular injury induced by this carcinogen.

Section: Discussionsupporting

confidence: 65%

Section: Discussionmentioning

confidence: 53%

See 1 more Smart Citation

Evaluation of Dimethylhydrazine Induced Tumours in Mice as a Model System for Colorectal Cancer

Haase¹,

Cowen²,

Knowles³

et al. 1973

“…Similar evidence of a generalized change in the mucosa adjacent to tumours in man, together with a decrease in the amount of sulphated mucopolysaccharides in these areas, has been suggested by Filipe (1971,1972). Springer, Springer and Oehlert (1970) also found an overall reduction of 35S uptake by the mucosa in those parts of the rat colon where tumours are commonly developed.…”

Section: Discussionmentioning

confidence: 67%

Glycosidases in Normal and Dimethylhydrazine-Treated Rats and Mice with Special Reference to the Colonic Tumours

Mian¹,

Cowen²

1974

Summary.-Activities of 12 glycosidases and of P-D-glucuronidase were measured in liver, kidney and in the gastrointestinal tract of rats and mice. The activities of different enzymes varied not only within one tissue but also among different tissues. In rats injected with 1,2 -dimethylhydrazine, a many fold increase indase and a-L-fucosidase was fountl in colonic tumours and colonic mucosa. These enzymes were elevated significantly in the kidney of tumour bearing animals as well. Liver and other parts of the gastrointestinal tract showed an increase only in N-acetyl-hexosaminidase with the appearance of colonic tumours. In treated mice, 2 N-acetylhexosaminidases were elevated in colon, duodenum, liver and kidney. However, in liver and kidney, P-D-galactosidase was also significantly increased.

“…Evidence of a generalized change, as indicated by an overall reduction of 35S uptake, in parts of the DMH treated rat colon where tumours were commonly developed has been given (Springer, Springer and Oehlert, 1970). The site where tumours would arise in the mouse colon after DMH treatment could be predicted with great certainty (Haase et al, 1973).…”

mentioning

confidence: 99%

Glycosidases Heterogeneity Among Dimethylhydrazine Induced Rat Colonic Tumours

Mian¹,

Cowen²,

Nutman³

1974

Summary.-Activities of N-acetyl-fl-D-glucosaminidase, N-acetyl-fl-D-galactosaminidase, 3-D-galactosidase and a-L-fucosidase were measured in rat colonic tumours induced by 1,2-dimethylhydrazine. Tumours varied considerably in their enzyme content, not only from different animals but also from the same animals. Enzymatic heterogeneity among tumours appeared to be related to their site of origin in the colon. The descending colon, which after the DMH treatment showed a significant increase in the levels of glycosidases, also gave rise to a larger number of adenocarcinomata than other parts of the colon. The relative changes in the activities of four glycosidases seemed to show a good correlation.IN GENERAL, rat colonic tumours induced bv 1,2-dimethylhydrazine (DM1H) indicated a significant increase in the levels of some glycosidases compared with the remaining colonic mucosa of the treated animals (Mian and Cowen, 1974). Evidence of a generalized change, as indicated by an overall reduction of 35S uptake, in parts of the DMH treated rat colon where tumours were commonly developed has been given (Springer, Springer and Oehlert, 1970). The site where tumours would arise in the mouse colon after DMH treatment could be predicted with great certainty (Haase et al., 1973). These authors observed that in the experimental mice the last 4 cm of the colon was always the site of at least one polyp. A gradient in the cell turnover times from the proximal to the distal end of the colon and a considerable variation in the cell proliferation rates in the DMH induced mouse colonic tumours and in the primary adenocarcinomata of the human large bowel have already been observed (Sawicki and Rowinski, 1970;Haase et al., 1973;Bottomley and Cooper, 1973;Camplejohn, Bone and Aherne, 1973).The present work was carried out to assess the enzymatic heterogeneity among the DMH induced rat colonic tumours with reference to the site specificity and variations in tumour morphology and cell kinetics. MATERIALS AND METHODSAnimals.-Wistar male rats, about 12 weeks old, were obtained from Bantin and Kingman, Hull, England. The animals were fed Oxoid 41B (Oxo Ltd, London, England) and water ad libitum. The experimental animals were injected subcutaneously for 26-32 weeks with a weekly dose of 20 mg/kg body weight of 1,2-dimethylhydrazine dihydrochloride (DMH) in 4% solution of Na2.EDTA made freshly each time as described by Haase et al. (1973). The control animals were given Na2. EDTA in saline solution. Injection of animals was stopped one week before they were used for the experiment.Preparation of tissue homogenates.-Animals were starved overnight before the experiment but had unrestricted access to water. They were killed by cervical dislocation. Colons were removed, opened by a longitudinal slit and washed with ice cold saline. Total length of the colon, location of the tumours and their number were recorded. Tumours were excised and kept individually. The remaining colons of the tumour bearing animals and the control colons were cut into 8 equ...