Open AccessChemoprevention by Pravastatin, a 3‐Hydroxy‐3‐methylglutaryl‐coenzyme A Reductase Inhibitor, of N ‐Methyl‐ N ‐nitrosourea‐induced Colon Carcinogenesis in F344 Rats
Author(s) -
Narisawa Tomio,
Morotomi Masami,
Fukaura Yoko,
Hasebe Makiko,
Ito Michiko,
Aizawa Rika
Publication year - 1996
Publication title -
japanese journal of cancer research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 0910-5050
DOI - 10.1111/j.1349-7006.1996.tb02103.x
Subject(s) - azoxymethane , anticarcinogen , endocrinology , pravastatin , medicine , carcinogenesis , reductase , chemistry , cholesterol , carcinogen , hydroxymethylglutaryl coa reductase , coenzyme a , hmg coa reductase , biochemistry , enzyme , cancer
A potential chemopreventive action of pravastatin (Pr), a 3‐hydroxy‐3‐methylglutaryl‐coenzyme A redutase inhibitor, on colon carcinogenesis was evaluated in F344 rats. All rats at 7 weeks of age received an intrarectal dose of 2 mg of N ‐methyl‐ N ‐nitrosourea 3 times weekly for 2 weeks in experiment I (2 groups of 16 rats each), and for 3 weeks in experiment II (4 groups of 30 rats each). They were given drinking water containing 0 ppm (control) or 200 ppm Pr during weeks 1 to 40 in experiment I, and containing 0 ppm (control), 25 ppm, 5 ppm and 1 ppm Pr during weeks 4 to 40 in experiment II. The body weight gains, and food and water intakes were similar in all the groups. The incidence of colon carcinomas at termination of the experiment at week 40 was not different in the 200 ppm Pr and control groups in experiment I (63% vs. 69%), while it was significantly lower in the 25 ppm and 5 ppm groups, but not in the 1 ppm Pr group, compared with the control group in experiment II (50%, 48%, and 77% vs. 80%). This inhibitory effect of Pr against colon carcinogenesis was not related to the cholesterol‐lowering effect of this agent. We postulate that Pr inhibits the promotion stage of colon carcinogenesis, perhaps through modulation of cholesterol synthesis in situ in the colonic mucosa, thereby suppressing farnesyl isoprenylation of growth‐regulating proteins such as p21 ras.