Tumors produced in rats with a single dosage of 1,2-dimethylhydrazine

Abstract

To evaluate possible nephroblastoma induction in young Sprague-Dawley male rats by 1,2-dimethylhydrazine (DMH), agents including inhibitors and stimulators of the carcinogenesis were tested concurrently in 2 experiments. In series A, rats, 27 days of age, were fed the following as supplements in a basal diet at the final wt% given: hydralazine (0.035%), disulfiram (250 ppm), ferrous sulfate heptahydrate (0.55%; 0.11 g% Fe), isotretinoin (240 ppm), dehydroepiandrosterone (0.30%) in addition to selenium (2 ppm; drinker). At day 15, DMH was injected s.c. at 108 mg base/kg; duration on the diets: 51 weeks. Series B comprised 33 day-old males which were partially hepatectomized (control and indomethacin at 10 mg/l by drinker) or bilaterally gonadectomized for comparison vs sham-operated, and intact groups on s.c. injection of estradiol benzoate (15 micrograms/kg), progesterone (30 mg/kg) and diallyl sulfide (100 mg/kg), the respective controls receiving the peanut oil vehicle. Treatments were begun 8 days post-operative and 17 days later, the single dosage of DMH as in the above was injected. The oil solutions were administered at the specified weekly levels for a total of 52 injections, 2 doses being introduced per week for the 1st 3 weeks. Colon adenocarcinomas comprised the main tumors and occurred in about 15-50% of the rats with total frequencies in the respective control ranges except for decrements with the disulfiram- and iron-fed groups. Renal changes were more involved with series B and nephroblastomas of the left kidney occurred in one animal each of the estradiol benzoate- and diallyl sulfide-injected groups. Of interest, bilateral nephroblastomas were present in one of the saline-injected controls which was gonadectomized. Under the conditions explored, concurrent treatment with DMH inhibitors or synergists had a minimal effect on nephroblastoma induction.