Action of estrogen and adrenocorticoids on adenocarcinoma induction by 1,2-dimethylhydrazine in male rats

Abstract

Groups of male Sprague-Dawley rats at 39 days of age, were injected s.c. with estradiol benzoate (15 micrograms/kg), cortisone acetate (2.5 mg/kg) and deoxycorticosterone acetate (10.0 mg/kg) in peanut oil, the controls receiving the oil vehicle on days 1 and 3 and weekly thereafter for a total of 32 injections. 1,2-Dimethylhydrazine was administered s.c. weekly after the 1st 2 drug doses, the dosage as base being 9.0 mg/kg for the 1st 7 injections, then 19.4 mg/kg for the last 13 dosages. The rats were killed 31 weeks after the 1st DMH injection. The changes in animal condition at necropsy were moderate to extreme in half of the rats and all survived the 20 DMH injection-schedule; mortality was low per group but elevated with the deoxycorticosterone acetate treatment (40%). Essentially all rats displayed colon adenocarcinomas and the total frequency and the number in the proximal and distal portions were in the control ranges except for the statistically significant decrements in overall and distal colon numbers for the estrogen-treated group and possibly, near-significance in case of the cortisone acetate-injected rats. Small intestinal adenocarcinomas which were more prevalent in the upper areas occurred among the groups. As based on the current findings with estrogen, the trend was in the direction of an inhibiting effect on DMH tumorigenesis in contrast to a stimulatory response reported for androgenized males.