Sequential histochemical and morphometric studies on preneoplastic and neoplastic lesions induced in rat colon by 1 ,2-dimethylhydrazine

Abstract

The sequential histochemical changes during colon carcinogenesis were studied in male Sprague-Dawley rats given 16 weekly subcutaneous injections of 15 mg 1,2-diinethyl- hydrazine per kg body wt and serially killed at regular in tervals. Cryostat sections were used to study the mucus content of the colonic mucosa with the periodic acid Schiff's reaction, and enzyme histocheinical methods were applied to investigate the activity of some key enzymes of carbohydrate metabolism at different stages of carcinogenesis. Enlarged mucus-rich crypts with a marked hypercellularlty (149% of control as determined morpbometrically) appearing very early during carcinogenic treatment revealed almost normal activities of glucose-6-phosphatase (G6Pase), glucose-6-phosphate dehydrogenase (G6PDH) and glyceraldehyde 3-phosphate dehydrogenase (GAPDH). Hyperbasophllic crypts lacking mucus production were observed later and showed a loss of G6Pase, but marked increase of G6PDH and GAPDH activity. Mucus-rich signet ring cell carcinomas showed the same enzymatic pattern as the mucus-rich crypts, whereas mucus-free adenocarcinomas and undifferentiated carcinomas revealed a loss of G6Pase and highly increased G6PDH and GAPDH activities. The results showed that focal changes in polysaccharide content and in the activity of some enzymes of carbohydrate metabolism, as observed in various organs, also accompany the carcinogenic process in the colon. This supports the concept that aberrations in carbohydrate metabolism play an important role during the process of carcinogenesis.