Induction of rat intestinal carcinogenesis with single doses, low and high repeated doses of 1,2-dimethylhydrazine.
We investigated seven different procedures for chemical induction of rat colonic carcinogenesis using: repeated high doses (i) weekly 10 x 15 mg/kg, (ii) quarterly 8 x 15 mg/kg; repeated low doses (iii) weekly 27 x 1.5 mg/kg, (iv) quarterly 8 x 5 mg/kg, (v) quarterly 8 x 1 mg/kg; and single injections of 1,2-dimethylhydrazine (DMH) at (vi) 1 x 40 mg/kg or (vii) 1 x 20 mg/kg. Rats had typical histological precancerous lesions of the colon (dysplasia) and intestinal carcinomas in the six groups receiving a total dose of more than 8 mg/kg DMH. With doses of greater than 120 mg/kg, rats had more cancers, particularly intestinal carcinomas and significantly reduced survival. Rats receiving a single injection of 20 or 40 mg/kg also had histological lesions and colonic carcinomas. The group receiving a 40 mg/kg total dose in a single injection had a significantly higher frequency of colonic lesions per rat and a higher incidence of rats with colonic lesions than groups receiving the same total dose but fractionated. Control rats and groups injected with an 8 mg/kg total dose had no cancers, nor pre-cancerous histological lesions. Thus the carcinogenesis is dose-related, but for the same final dose a single injection gives more histological colonic lesions than several recurrent injections; however, the number of colonic carcinomas and the survival did not vary. This lack of correlation between the number of dysplasia and the number of adenocarcinomas may indicate that dysplasia is not always the precursor lesion of adenocarcinoma. With repeated low doses, we obtained colonic adenocarcinomas after a long period of latency in old rats, thus producing an experimental model with characteristics similar to those found in humans.
Decaens
C
C
Laboratoire d'Immunochimie, IRSC, Villejuif, France.
Gautier
R
R
Daher
N
N
Bara
J
J
Burtin
P
P
D019813:1,2-Dimethylhydrazine; D000818:Animals; D002277:Carcinoma / Q000139:chemically induced* / Q000473:pathology; D004127:Dimethylhydrazines / Q000008:administration & dosage* / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D007413:Intestinal Mucosa / Q000473:pathology; D007414:Intestinal Neoplasms / Q000139:chemically induced* / Q000473:pathology; D008297:Male; D008763:Methylhydrazines / Q000008:administration & dosage*; D051381:Rats; D011919:Rats, Inbred Strains
D004127:Dimethylhydrazines; D008763:Methylhydrazines; D019813:1,2-Dimethylhydrazine