An investigation into the mechanism of co-carcinogenesis of dietary cholesterol during the induction of colon cancer in rats by 1,2 dimethylhydrazine.
The mechanism by which dietary cholesterol facilities colon carcinogenesis was investigated in the dimethylhydrazine-induced rat colon cancer model. Fifty female Wistar rats received a standard course of dimethylhydrazine (DMH) injections (40 mg/kg/week subcutaneously for ten weeks) while being fed Vivonex, a cholesterol-free elemental diet. Animals were allocated to one of five dietary regimens. One control group received Vivonex with added cholesterol (10 mg/100 ml Vivonex/rat/day) throughout the experiment, while another group received Vivonex alone. The remaining three groups received added cholesterol exclusively before, during or after the ten week DMH induction period. The experiment continued for over 500 days, and was evaluated by comparing, between groups, the time taken for the development of objective signs of colonic disease (time to tumour presentation or TTP). Animals either died spontaneously or were killed and autopsied. Colon cancers were confirmed histologically in every animal. The results showed that cholesterol feeding throughout the experiment or during the DMH induction period reduced the TTP compared to controls (p less than 0.05). Cholesterol prefeeding had no such effect. In the after group, the TTP was correspondingly delayed (p less than 0.05). Cholesterol-fed controls and groups receiving cholesterol during or after the DMH induction had more colon tumours and/or a greater incidence of metastases than cholesterol-free controls or those pre-fed cholesterol. The findings indicate a direct relationship between timing of cholesterol exposure and signs of colon cancer, and demonstrate that dietary cholesterol has promoter-like characteristics.
D019813:1,2-Dimethylhydrazine; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002273:Carcinogens; D002791:Cholesterol, Dietary / Q000009:adverse effects*; D003110:Colonic Neoplasms / Q000209:etiology* / Q000473:pathology; D004127:Dimethylhydrazines / Q000633:toxicity*; D005260:Female; D008763:Methylhydrazines / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D002273:Carcinogens; D002791:Cholesterol, Dietary; D004127:Dimethylhydrazines; D008763:Methylhydrazines; D019813:1,2-Dimethylhydrazine