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

Abstract

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.

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

“…An increase in the activity of these enzymes could possibly enhance the catabolism of carbohydrate containing macromolecules. It may also explain the lack of PAS or alcian blue staining in the sections of colonic tumours (Rogers et al, 1973;Haase et al, 1973).…”

“…The rats and mice were given a weekly dose of 20 mg and 20 mg per kg body weight, respectively. The DMH solution was freshly made up in sodium EDTA solution each time as described previously (Haase et al, 1973). The control animals were injected with sodium EDTA in saline alone.…”

“…An elevation of certain glycosidases in fibroblasts transformed by oncogenic viruses (Bosmann, , 1972 and in the sera of patients with carcinoma of the lung, stomach, prostate and breast (Goldbarg et al, 1959;Woollen and Turner, 1965;Ayoub, 1967) have been reported. The present work has been carried out to study the normal distribution of glycosidases and fi-D-glucuronidase in various rat and mouse tissues, and to investigate the effect of 1,2-dimethylhydrazine dihydrochloride (DMH) on these enzymes since this carcinogen has been found to produce rat colonic tumours and mouse colonic adenomatous polyps which have a characteristic loss of mucopolysaccharides (Rogers, Herndon and Newberne, 1973;Haase et al, 1973).…”

Glycosidases Heterogeneity Among Dimethylhydrazine Induced Rat Colonic Tumours

“…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. …”

“…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.…”