THE PROGRESSION OF 1,2-DIMETHYLHYDRAZINE-INDUCED COLON TUMORIGENESIS STIMULATES GROWTH AND CELL-PROLIFERATION IN THE COLON OF THE HOST MOUSE

The aim of this study was to characterize tissue responses attributable to the stage of tumourigenesis in CF-1 mice. The study involved initiating colon carcinogenesis by eight weekly subcutaneous injections of 1,2-dimethylhydrazine (DMH at 12 mg/kg body weight), while the control mice received injections of the carrier vehicle. All mice were killed for examination of tissue responses at 24 weeks after the completion of the injections. Each mouse was classified into one of four groups based on the histology of the most advanced colonic lesion. The four groups or stages were: 1 no lesions (non-DMH-treated mice); 2 mice with aberrant crypt foci (ACF); 3 mice with one or more adenomas (AD) and 4 mice with an adenocarcinoma (AC). Significant tissue specific responses were identified and related to the stage of tumourigenesis. For example, mice with AC demonstrated a stage specific and marked hypertrophy of the entire colon and spleen, while demonstrating loss of body weight with no change in weight of the thymus or liver. The colonic crypts from these AC-bearing mice demonstrated hyperproliferation and an upward shift of the proliferative zone, with a concurrent loss of iron, but not of calcium, copper, magnesium or zinc in the liver. Splenomegaly was attributed to transition of the tumour to an invasive state. It is proposed that the AC produces a blood-borne trophic factor which helps explain a field effect on the colonic epithelium far removed from the growing AC. This geld effect can help explain how biopsy of the large bowel (usually taken from the rectum in humans) can provide morphokinetic information predictive of the stage of colon carcinogenesis.