TUMORS PRODUCED IN RATS WITH A SINGLE DOSAGE OF 1,2-DIMETHYLHYDRAZINE

Citation
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
Citations number
39
Categorie Soggetti
Pharmacology & Pharmacy",Pathology
ISSN journal
00345164
Volume
80
Issue
2
Year of publication
1993
Pages
175 - 186
Database
ISI
SICI code
0034-5164(1993)80:2<175:TPIRWA>2.0.ZU;2-I
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 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.