Ornithine decarboxylase inhibitor attenuates bombesin enhancement of intestinal carcinogenesis and metastasis induced by azoxymethane.
The effects of combined administration of bombesin (40 micrograms/kg body weight) and the ornithine decarboxylase (ODC) inhibitor, 1,3-diaminopropane (DAP), on the development of large and small intestinal tumors and the incidence of their metastasis to the peritoneum induced by azoxymethane (AOM, 7.4 mg/kg body weight), the ODC activity of the intestinal wall, and the labeling index of the intestinal mucosa and tumor were investigated in inbred Wistar rats. Rats received weekly s.c. injections of AOM for 10 weeks, s.c. injections of bombesin every other day, and drinking water containing DAP (2.5 g/l) until the end of the experiment at week 40. Administration of bombesin significantly increased the incidence of intestinal tumors at week 40. It had no influence on the location, size, histological features or depth of involvement of intestinal adenocarcinomas, but significantly increased the incidence of their metastasis to the peritoneum. It also resulted in a significant increase in the intestinal ODC activity and labeling index. Administration of DAP with bombesin significantly reduced the enhancement of intestinal carcinogenesis by bombesin. Although the combined use of DAP with bombesin had little or no influence on the location, size, histological features, or depth of involvement of intestinal cancers, the incidence of their metastasis was significantly reduced. DAP significantly attenuated bombesin enhancement of the intestinal ODC activity and labeling index. These findings indicate that ODC inhibition attenuated the enhancement of intestinal carcinogenesis and metastasis to the peritoneum.
Iishi
H
H
Department of Gastrointestinal Oncology, Center for Adult Diseases, Osaka, Japan.
Tatsuta
M
M
Baba
M
M
Uehara
H
H
Nakaizumi
A
A
D000230:Adenocarcinoma / Q000139:chemically induced; D000818:Animals; D001397:Azoxymethane; D001835:Body Weight; D001839:Bombesin / Q000494:pharmacology*; D002455:Cell Division; D003959:Diamines / Q000494:pharmacology*; D004357:Drug Synergism; D005755:Gastrins / Q000097:blood; D007413:Intestinal Mucosa / Q000201:enzymology; D007414:Intestinal Neoplasms / Q000139:chemically induced* / Q000201:enzymology; D008297:Male; D009362:Neoplasm Metastasis; D065108:Ornithine Decarboxylase Inhibitors; D010534:Peritoneal Neoplasms / Q000556:secondary; D051381:Rats; D017208:Rats, Wistar
D003959:Diamines; D005755:Gastrins; D065108:Ornithine Decarboxylase Inhibitors; C009475:trimethylenediamine; D001397:Azoxymethane; D001839:Bombesin