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.