DNA aneuploidy and proliferation in spontaneous human and dimethylhydrazine-induced murine colorectal carcinogenesis

DNA aneuploidy and proliferative abnormalities were studied by flow cytometry in 169 colorectal specimens from 162 patients. Of 37 adenomas, three showed aneuploidy and another seventeen revealed a "near diploid" DNA pattern. The rate of aneuploid and "near diploid" DNA changes in 92 carcinomas was 53.3% and 23.9%, respectively. No correlation was seen between the ploidy distribution and the stage or histologic grade of the carcinomas. The S-phase fractions of both adenomas and carcinomas significantly increased from the diploid (8.1 +/- 0.8% and 7.8 +/- 0.9% respectively; mean +/- SEM) to the "near diploid" (14.9 +/- 1.2% and 12.6 +/- 1.5%) and aneuploid (20.4 +/- 1.3% and 11.4 +/- 1.6%) lesions. To better understand neoplastic progression at very early stages, flow cytometry was also performed on 195 colonic specimens of 44 rats treated by weekly subcutaneous injections of 21 mg/kg Dimethylhydrazine. There was a single "near diploid" carcinoma in this group, and all other induced neoplasms (39 carcinomas and 27 adenomas) revealed a diploid DNA pattern. The S-phase fractions were as follows: controls (38 untreated animals) 8.6 +/- 0.1%, normal mucosa (of Dimethylhydrazine exposed rats) 10.1 +/- 0.25% (p less than 0.0001), adenomas 13.9 +/- 0.6% (p less than 0.01), and carcinomas 14.7 +/- 0.6% (p less than 0.01). These findings support the conclusion that genomic alterations and proliferative abnormalities may already be present in premalignant human colonic lesions. However, despite strong morphological similarities, major biological differences exist between the Dimethylhydrazine-induced murine intestinal carcinogenesis and spontaneously occurring human colorectal neoplasms.