ras p21 Isoprenylation inhibition induces flat colon tumors in Wistar rats.
OBJECTIVE
The effect of pravastatin, an inhibitor of ras p21 isoprenylation, on the gross type of colon tumors induced by azoxymethane was investigated in Wistar rats.


METHODS
Rats received ten weekly subcutaneous injections of 7.4 mg/kg body weight of azoxymethane and intraperitoneal injections of 10 or 20 mg/kg body weight of pravastatin every other day until the end of the experiment at Week 45.


RESULTS
Administration of pravastatin at both dosages had no significant effect on the incidence of colon tumors but significantly increased the incidence of rats with adenomas only. In contrast to the elevated adenomas in control rats, flat adenomas were significantly more prevalent in rats given pravastatin. Pravastatin at both doses significantly decreased the labeling index, but not the apoptotic index, of elevated adenomas, whereas it significantly decreased the labeling index but increased the apoptotic index of flat adenomas. Administration of pravastatin at both dosages also significantly decreased the amounts of membrane-associated ras p21 in colon tumors.


CONCLUSIONS
These findings suggest that the ras oncogene may be closely related to the development of adenocarcinomas from adenomas and the development of elevated or polypoid tumors of the colon.
Iishi
H
H
Department of Gastrointestinal Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Japan.
Tatsuta
M
M
Baba
M
M
Yano
H
H
Sakai
N
N
Uehara
H
H
Nakaizumi
A
A
D000230:Adenocarcinoma / Q000139:chemically induced / Q000235:genetics / Q000473:pathology; D000236:Adenoma / Q000139:chemically induced / Q000235:genetics / Q000473:pathology; D000704:Analysis of Variance; D000818:Animals; D000963:Antimetabolites; D017209:Apoptosis / Q000187:drug effects; D001397:Azoxymethane / Q000008:administration & dosage / Q000009:adverse effects*; D015153:Blotting, Western; D001973:Bromodeoxyuridine; D002273:Carcinogens / Q000008:administration & dosage / Q000009:adverse effects*; D003110:Colonic Neoplasms / Q000139:chemically induced* / Q000235:genetics / Q000473:pathology; D003111:Colonic Polyps / Q000139:chemically induced / Q000235:genetics / Q000473:pathology; D011905:Genes, ras / Q000235:genetics; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D015994:Incidence; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D008297:Male; D015689:Oncogene Protein p21(ras) / Q000037:antagonists & inhibitors*; D017354:Point Mutation / Q000235:genetics; D017035:Pravastatin / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D015995:Prevalence; D017368:Protein Prenylation / Q000187:drug effects*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar
D000963:Antimetabolites; D002273:Carcinogens; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D015689:Oncogene Protein p21(ras); D001973:Bromodeoxyuridine; D017035:Pravastatin; D001397:Azoxymethane