Faecal mutagens and intestinal tumours in the dimethylhydrazine-injected rat

The relationship between the development of colonic tumours and the presence of faecal mutagens has been investigated in the dimethylhydrazine (DMH) injected rat model. Subcutaneous DMH 20 mg/kg for 6 weeks in 10 rats produced colonic tumours in 8 animals and duodenal tumours in 2. Faeces were collected 6, 10, 14, 20 and 25 weeks after commencing DMH injections and were assayed using the Ames test system with both aqueous and ether extracts. All faeces were initially negative for mutagens, but all became positive at some stage following DMH injections, There was no consistent pattern of mutagen excretion or of the strain of Salmonella typhimurium detecting a positive extract. Early positive extracts tended to be with aqueous extracts, whereas later extracts (20 and 25 weeks) were predominantly with ether extracts. DMH produces a metabolic change in the rat resulting in the production of faecal mutagens. This change precedes the appearance of colonic neoplasms and persists after the withdrawal of DMH injections.