Carcinogenicity of 1,2-dimethylhydrazine in colorectal tissue heterotopically transplanted into the glandular stomach of rats

Abstract

The present study was designed to examine the effect of the intestinal carcinogen 1,2-dimethylhydrazine (DMH) on grafted colorectal mucosa implanted into the glandular stomach of rats. Four groups were studied: Group 1 received the operation and DMH, Group 2 received the operation alone, Group 3 received DMH alone and Group 4 (controls) received only a sham operation. For Groups 1 and 2, about 8-mm diameter segments of colorectal tissue obtained from various sites in the large intestine of 8-week-old male F344 rats were isologously implanted into the fundic region of the stomachs of age-matched rats. DMH was injected at a dose of 20 mg/kg body weight i.m. per week for 20 weeks beginning 4 weeks after the operation. The animals were then observed for 8 months after the initial DMH treatment. In Group 1, adenocarcinomas developed in 41 of 60 successful implants (68%). Furthermore, poorly differentiated type tumors were observed in the grafts obtained from the rectum. This finding was contrary to that for intrinsic rectal tumors, all of which were well differentiated. The histochemical staining of mucin in the tissues from different sites of the large intestine revealed that sulfomucin, which normally exists essentially only in the intrinsic descending colon or rectum, was present in the grafts from the proximal ascending or ascending colon. No gastric tumors were observed in the control rats, which received either DMH or sham operations alone. Tumors in the intrinsic large intestine were observed only in rats that received DMH. These results indicate that colorectal mucosa implanted into the glandular stomach, like the intrinsic large intestine, is still sensitive to tumorigenesis caused by DMH.