COLONIC CRYPTS LOCATED OVER LYMPHOID NODULES OF 1,2-DIMETHYLHYDRAZINE-TREATED RATS ARE HYPERPLASTIC AND AT HIGH-RISK OF FORMING ADENOCARCINOMAS

Male, Sprague-Dawley rats were injected subcutaneously with the colon carcinogen 1,2-dimethylhydrazine (DMH) at a dosage of 9.5 mg DMH base/ per kg rat body weight once weekly for 8 weeks; control rats received an equivalent volume of the vehicle. Analyses of variance showed that in carcinogen-treated as well as in non-carcinogen-treated rats, the p roliferative zone height and the crypt height in colonic crypts locate d over the aggregates of lymphoid nodules (ALN) were significantly hig her than in colonic crypts located away from the ALN. Immunohistochemi cal localization of transforming growth factor a (TGF alpha) showed th at this mitogenic factor was found in cells in the proliferative zone of colonic crypts located over the ALN, but TGF alpha was not detectab le in cells in the proliferative zone of colonic crypts located away f rom the ALN. Examination of histological sections of the colon taken t hrough the ALN of DMH-treated rats revealed that eight out of 25 DMH-t reated rats had microscopic adenocarcinomas (AC) within the ALN, but i n the same rats no microscopic AC were seen in histological sections t aken away from the ALN. Furthermore, there was no evidence of an adeno matous precursor to these microscopic, endophytic AC, suggesting that the endophytic AC arose de novo. Therefore, because of (i) the signifi cantly higher proliferative activity in colonic crypts located over th e ALN, (ii) the localization of TGF alpha in the proliferative zone of the colonic crypts associated with ALN and (iii) the high incidence o f endophytic AC associated with ALN, it seems likely that factors eman ating from the ALN are promotional to carcinogenesis in the colonic ep ithelium that is located in close proximity to the ALN.