ATTENUATION OF VASOACTIVE-INTESTINAL-PEPTIDE ENHANCEMENT OF COLON CARCINOGENESIS BY ORNITHINE DECARBOXYLASE INHIBITOR

The effects of combined administration of vasoactive intestinal peptid e (VIP) and the ornithine decarboxylase (ODC) inhibitor, 1,3-diaminopr opane (DAP), on development of colon tumors induced by azoxymethane (A OM), on ODC activity of the colon wall, and on the labelling index of colon epithelial cells were investigated in inbred Wistar rats. Rats r eceived weekly subcutaneous injections of AOM for 10 weeks and subcuta neous injections of VIP every other day and drinking water containing DAP (2.5 g/l) ad libitum until the end of the experiment at week 45. A dministration of VIP significantly increased the incidence of colon tu mors at week 45. It also resulted in significant increases in colon OD C activity and in the labelling index during administration of AOM, bu t not after its cessation. Administration of both DAP and VIP signific antly reduced the enhanced colon carcinogenesis by VIP. The DAP signif icantly attenuated the VIP enhancement of colon ODC activity and of th e labelling index during AOM administration. These findings indicate t hat ODC inhibition attenuated enhancement of colon carcinogenesis, and suggest that enhancement of colon carcinogenesis by VIP may be mediat ed through its polyamine biosynthesis.