The influence of anticoagulants on the development of colorectal cancer in the rat and their activity in human colorectal cancer

Goeting, Nicola Laura Margaret (1986) The influence of anticoagulants on the development of colorectal cancer in the rat and their activity in human colorectal cancer. University of Southampton, Doctoral Thesis.

Abstract

Pre-neoplastic changes were studied in an animal model for chemically induced colorectal cancer. This included cell kinetic and morphological changes, demonstrated by stathmokinetic techniques and scanning electron microscopy (SEM). The effects of warfarin [3-(a-acetonylbenzyl)-4-hydroxycoumarin] on these aspects, and tumour size and incidence were studied. These studies investigated the mechanism by which warfarin affects the development of malignancy. It was adminstered at low dose (non-therapeutic anticoagulation) and at high dose (therapeutic anticoagulation). In stathmokinetic studies the crypt cell production rate (CCPR), a cell kinetic index, was determined. The CCPR in normal animals was highest in the caecum, intermediate in descending and ascending colon, and lowest in transverse colon and rectum. With carcinogenesis CCPR increased in all areas; the greatest increase occurred in the distal colon and the smallest in the caecum. Maximum tumour yield also occurred in descending colon and rectum. Warfarin, at either dose, had no significant effect on CCPR. However tumour incidence was significantly decreased by both doses. SEM demonstrated small raised areas on the epithelial surface. Conventional histololgy demonstrated that they had adenomatous characteristics. These `microadenomas

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