Acute changes occurring in the intestinal mucosae of rats given a single injection of 1,2 dimethylhydrazine
Tóm tắt
In the long term, administration of dimethylhydrazine (DMH) to rats results in the development of tumours in both small intestine and colon. This study has been undertaken in order to document the sequence of changes occurring in the intestinal mucosa in the first 108 h following a single subcutaneous injection of DMH. After a lag of several hours there is evidence of damage to cells in the proliferation zone of the intestinal crypts, and a brief reduction in tritiated thymidine labelling index. A phase of compensatory regenerative activity emerges from the setting of continuing cell damage, resulting in restoration of the mucosa to normal. The severity of the toxic damage to the intestinal mucosa at various sites mirrors the vulnerability of the mucosa to the long term carcinogenic effects of DMH, suggesting that inherent properties of the mucosa may be of more importance than other cocarcinogenic influences in the ultimate development of tumours.
Tài liệu tham khảo
Al-Dewachi HS, Wright NA, Appleton DR, Watson AJ (1976) Studies on the mechanism of diurnal variation of proliferative indices in the small bowel mucosa of the rat. Cell Tiss Kinet 9:459–467
Cairnie AB, Bentley J (1967) Cell proliferation studies in the intestinal epithelium of the rat. Hyperplasia during lactation. Exp Cell Res 46:428–440
Castleden WM, Shilkin KB (1979) Diet, liver function and dimethylhydrazine induced gastrointestinal tumours in male Wistar Rats. Br J Cancer 39:731–739
Deschner, E.E. (1978) Early proliferative defects induced by six weekly injections of 1,2-dimethylhydrazine in epithelial cells of mouse distal colon. Z Krebsforsch 91:205–216
Druckrey H (1970) Production of colonic carcinomas by 1,2 dialkylhydrazines and azoxyalkanes. In: Burdette JW (ed) Carcinoma of the colon and antecedent epithelium. Charles C Thomas, Springfield Illinois, pp 267–279
Druckrey H, Preussman R, Matzkies F, Ivankovic S (1967) Selektive Erzeugung von Darmkrebs bei Ratten durch 1,2 Dimethylhydrazin. Naturwissenschaften 54:285–286
Gennaro AR, Villanueva R, Sukonthaman Y, Vathanophas V, Rosemond GP (1973) Chemical carcinogenesis in transposed intestinal segments. Cancer Res 33:536–541
Grab DJ, Zedeck MS (1977) Organ-specific effects of the carcinogen methylazoxymethanol related to metabolism by nicotinamide adenine dinucleotide dependent dehydrogenases. Cancer Res 37:4182–4189
Hamilton E (1980) Diurnal variation in proliferation of ‘cryptogenic’ and ‘amplification’ cells in mouse descending colon: a comparison of two inbred mouse strains. In: Appleton DR, Sunter JP, Watson AJ (eds) Cell proliferation in the gastrointestinal tract. Pitman Medical Publishing Co., Tunbridge Wells, pp 166–177
Hawks A, Hicks RM, Holsman JW, Magee PN (1974) Morphological and biochemical effects of 1,2 dimethylhydrazine and 1 methylhydrazine in rats and mice. Br J Cancer 30:429–439
Lindström CG, Rosengren JE, Ekberg O (1978) Experimental colonic tumours in the rat. III Induction time, distribution and appearance of induced tumours. Acta Radiol Diag 19:799–816
Loehrs U, Wiebecke B, Eder M (1969) Morphologische und Autoradiographische Untersuchung der Darmschleimhautveränderungen nach einmaliger Injektion von 1,2-Dimethylhydrazin. Z Ges Exp Med 151:297–307
Martin MS, Martin F, Michiels R, Bastien H, Justrabo E, Bordes M, Viry B (1973) An experimental model for cancer of the colon and rectum. Digestion 8:22–34
Maskens AP (1976) Histogenesis and growth pattern of 1,2 dimethlhydrazine induced rat colon adenocarcinoma. Cancer Res 36:1585–1592
Nomura K, Schlake W, Grundmann E (1978) New aspects of intestinal carcinogenesis by 1,2 dimethylhydrazine dihydrochloride (DMH) and the influence of antilymphocytic globuline (ALG) on its progress. Z Krebsforsch 92:17–33
Pozharisski KM (1975) Morphology and morphogenesis of experimental epithelial tumours of the intestine. J Nat Canc Inst 54:1115–1135
Sunter JP, Appleton DR, Wright NA, Watson AJ (1978a) Kinetics of changes in the crypts of the jejunal mucosa of dimethlhydrazine treated rats. Br J Cancer 37:662–672
Sunter JP, Appleton DR, Wright NA, Watson AJ (1978b) Pathological features of the colonie tumours induced in rats by the administration of 1,2 dimethylhydrazine. Virchows Arch [Cell Pathol] 29:211–223
Sunter JP, Watson AJ, Wright NA, Appleton DR (1979) Cell proliferation at different sites along the length of the rat colon. Virchows Arch [Cell Pathol] 32:75–87
Ward JM (1974) Morphogenesis of chemically induced neoplasms of the colon and small intestine in rats. Lab Invest 30:505–513
Wright NA, Morley AR, Appleton DR (1972) Variation in the duration of mitosis in the crypts of Lieberkühn of the rat; a cytokinetic study using vincristine. Cell Tissue Kinet 5:351–364
Zedeck MS, Grab DJ, Sternberg SS (1977) Differences in the acute response of the various segments of rat intestine to treatment with the intestinal carcinogen methylazoxymethanol acetate. Cancer Res 37:32–36
Zedeck MS, Sternberg S, Poynter RW, McGowan J (1970) Biochemical and pathological effects of methylazoxymethanol acetate, a potent carcinogen. Cancer Res 30:801–812 (1970)