[The incidence of 1,2-dimethylhydrazine-induced colonic neoplasms in the rat: the effect of constipation].

The authors studied the role of slow bowel transit in the development of colonic neoplasias in rats treated with 1,2-dimethylhydrazine (DMH). Forty Sprague-Dawley male rats, weighing 400 g, were used in the experiment and were divided into 4 groups of 10 rats each. The first and the second group were given, weekly, subcutaneous injections of DMH at a dose of 25 mg/kg for 25 and 27 weeks respectively; in these groups constipation was obtained by reducing water intake throughout the period of the experiment. The third and the fourth group (control groups) received DMH at the dose of 25 mg/kg for 25 and 27 weeks respectively and water "ad libitum". The rats were weighed once a week and stool output, weight, and number of scybala/day were recorded once every four weeks. Rats were sacrificed one week after the final injection of DMH and every intestinal lesion macroscopically identified was histologically examined. All rats showed weight loss from the 22nd week to the sacrifice. The mean stool weight/day was 21.2 g +/- 1.47 in the groups A and B; while for the groups C and D it was 23.6 g +/- 1.81 (p = 0.019). The number of scybala/day was 26 +/- 3 in the groups A and B, whereas in the groups C and D was 34 +/- 4 (p = 0.05). An increased number of cancers per rat was recorded in the groups A and B compared to control groups, respectively from 0.66 to 1.4 at 25 weeks (p = 0.02) and from 0.9 to 2.44 at 27 weeks (p = 0.07). A corresponding increase in the number of polyps after 25 weeks was demonstrated, taking into account the possible polyp-cancer sequence. Our study suggests that the slow bowel transit induced an increased number of colonic neoplasia in relation to the prolonged contact of the carcinogen with the mucosa or to its greater concentration in the colonic lumen due to the fecal output reduction.