Ll. Gershbein et al., TUMORS PRODUCED IN RATS WITH A SINGLE DOSAGE OF 1,2-DIMETHYLHYDRAZINE, Research communications in chemical pathology and pharmacology, 80(2), 1993, pp. 175-186
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 ex
periments. In series A, rats, 27 days of age, were fed the following a
s 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 add
ition to selenium (2 ppm; drinker). At day 15, DMH was injected s.c. a
t 108 mg base/kg; duration on the diets: 51 weeks. Series B comprised
33 day-old males which were partially hepatectomized (control and indo
methacin at 10 mg/l by drinker) or bilaterally gonadectomized for comp
arison vs sham-operated, and intact groups on s.c. injection of estrad
iol benzoate (15 mug/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 si
ngle dosage of DMH as in the above was injected. The oil solutions wer
e administered at the specified weekly levels for a total of 52 inject
ions, 2 doses being introduced per week for the 1st 3 weeks. Colon ade
nocarcinomas comprised the main tumors and occurred in about 15-50% of
the rats with total frequencies in the respective control ranges exce
pt for decrements with the disulfiram- and iron-fed groups. Renal chan
ges were more involved with series B and nephroblastomas of the left k
idney occurred in one animal each of the estradiol benzoate- and diall
yl sulfide-injected groups. Of interest, bilateral nephroblastomas wer
e present in one of the saline-injected controls which was gonadectomi
zed. Under the conditions explored, concurrent treatment with DMH inhi
bitors or synergists had a minimal effect on nephroblastoma induction.