N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)誘発ラット大腸癌に関する病理学的研究
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Cytopathic and carcinogenic effects of intermittent intra-colic administration of 5mg MNNG (5mg/ml) daily for the first 3 days of a week on the rat large intestine were studied. The results were obstained as follows. 1) Degenerative changes such as cytoplasmic vacuolation and pyknosis in the surface epithelium of large intestine were found 1 hour after the MNNG administration. Deeper cells were also affected and complete erosion was preferentially formed in the large intestine between 2.0 and 8.0cm from anal ring 24 hours after 3 successive doses. 2) After the cessation of MNNG administration, erosions were repaired with epithelial cells around erosions and/or in the deep region of erosions within 4 days. 3) This damage- and repair-process were weekly repeated by the intermittent intra-colic administration of MNNG. 4) Continuation of this weekly damage- and repair-cycles rapidly and effectively induced adenocarcinomas of the large intestine. Cancers were preferentially producted in the same region as the erosions. The results suggest that the fundamental rule of chemical carcinogenesis which repeated tissue damage followed by regeneration provides a favorable condition for cancer induction is applied to the cancer induction in the large intestine by MNNG. 5) Cancers were rapidly and effectively induced in the experimental groups with higher doses of MNNG than the lower doses by this administration method. 6) From the precise observations of inducive process of cancers, it was considered that the majority (83%) of cancers were induced in the condition of "de novo" and that the minority (17%) were derived from adenomas. 7) The following characteristics of nuclear DNA-mode stained by Feulgen reaction were demonstrated in MNNG-induced cancers of the rat. (1) the main mode were widely distributed in (2) the histogram was unsymmetrical and consisted of multiple peaks. (3) cells more than 4C in DNA-content. were detected in high frequency. These characteristics offered the effective method for the identification of MNNG-induced cancers. 8) On the basis of the above results, growth process of cancers was presumed and discussed.
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- N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)誘発ラット大腸癌に関する病理学的研究