Modification of the carcinogenic process in colorectal cancer by endogenous and exogenous factors: effect of colestipol hydrochloride on tumors induced by dimethylhydrazine.
The effect of the bile acid sequestrant, colestipol hydrochloride, on the incidence of dimethylhydrazine-induced tumors of the large intestine was determined in male Swiss mice. The subcutaneous administration of dimethylhydrazine (15 mg/kg) produced tumors in approximately 89% of the animals with an average of 1.70 tumors per tumor-bearing animal. When carcinogen-treated animals received dietary colestipol (0.52%, w/w) from 4 weeks prior to the first injection of dimethylhydrazine until the time of death, there was an increase in the number of tumors per tumor-bearing animal to 2.23. In an attempt to understand the nature of this enhancement, animals were administered dietary colestipol at different times in relation to the administration of the carcinogen. The number of tumors per tumor-bearing animal for the different protocols was: post-initiation colestipol exposure, 1.70; colestipol exposure concomitant with dimethylhydrazine, 1.41; pre-initiation colestipol exposure, 2.23. Thus, colestipol appeared to function both as an anticarcinogen and as a promoter (pre-initiation). Since colestipol has the capacity to bind a number of chemical agents, the different biological effects probably reflect the multifactorial nature of colorectal cancer with the end result dependent on the balance between opposing factors. The selective administration of colestipol in relation to carcinogen administration may prove useful in elucidating the various factors involved in the etiology of this disease.
D000818:Animals; D002273:Carcinogens; D003043:Cocarcinogenesis; D003084:Colestipol; D003110:Colonic Neoplasms / Q000139:chemically induced*; D004127:Dimethylhydrazines; D008297:Male; D008763:Methylhydrazines; D051379:Mice; D011073:Polyamines; D012004:Rectal Neoplasms / Q000139:chemically induced*
D002273:Carcinogens; D004127:Dimethylhydrazines; D008763:Methylhydrazines; D011073:Polyamines; D003084:Colestipol