Species variation in response to dimethylhydrazine
Wilson, R.B.
Toxicology and Applied Pharmacology 38(3): 647-650
1976
ISSN/ISBN: 0041-008X PMID: 1014019 Document Number: 97501
In an attempt to develop a model of cancer of the colon in species other than rats, mice or hamsters, 1,2-dimethylhydrazine dihydrochloride (DMH) was administered intragastrically or s.c. to dogs (60, 30, 15 or 5 mg/kg), miniature swine (60 or 30 mg/kg) and guinea pigs (60 or 30 mg/kg). The animals were dosed at weekly intervals to a maximum of 10 times. The carcinogen was hepatotoxic in all 3 species and caused death of all animals except at the lowest dosage in each case. Toxicity was greatest in the dog. Survivors were observed for 18 mo. after final dosing. Hepatic fibrosis was observed in all surviving animals, but neither tumors of the digestive system nor of other systems were found, except in guinea pigs where bile duct cell carcinomas and hepatomas were observed in approximately half of the animals. As a positive control, DMH was administered to rats (30 mg/kg) once each week for 8 wk. All developed tumors of the colon as expected within 7 mo. Results of this preliminary study suggest marked differences in the metabolism of DMH among the various species. Colon tumors occurred only in the species (rat) showing the greatest tolerance for the carcinogen, although such tumors might have developed in the others (swine, dogs, guinea pig) had the observation period been longer.