Attenuation of vasoactive intestinal peptide enhancement of colon carcinogenesis by ornithine decarboxylase inhibitor.
The effects of combined administration of vasoactive intestinal peptide (VIP) and the ornithine decarboxylase (ODC) inhibitor, 1,3-diaminopropane (DAP), on development of colon tumors induced by azoxymethane (AOM), on ODC activity of the colon wall, and on the labelling index of colon epithelial cells were investigated in inbred Wistar rats. Rats received weekly subcutaneous injections of AOM for 10 weeks and subcutaneous injections of VIP every other day and drinking water containing DAP (2.5 milligrams) ad libitum until the end of the experiment at week 45. Administration of VIP significantly increased the incidence of colon tumors at week 45. It also resulted in significant increases in colon ODC activity and in the labelling index during administration of AOM, but not after its cessation. Administration of both DAP and VIP significantly reduced the enhanced colon carcinogenesis by VIP. The DAP significantly attenuated the VIP enhancement of colon ODC activity and of the labelling index during AOM administration. These findings indicate that ODC inhibition attenuated enhancement of colon carcinogenesis, and suggest that enhancement of colon carcinogenesis by VIP may be mediated through its polyamine biosynthesis.
Tatsuta
M
M
Department of Gastrointestinal Oncology, Center for Adult Diseases, Osaka, Japan.
Iishi
H
H
Baba
M
M
Yamamoto
R
R
Uehara
H
H
Nakaizumi
A
A
D000230:Adenocarcinoma / Q000139:chemically induced* / Q000378:metabolism; D002288:Adenocarcinoma, Mucinous / Q000139:chemically induced / Q000378:metabolism; D000236:Adenoma / Q000139:chemically induced / Q000378:metabolism; D000818:Animals; D001397:Azoxymethane; D003110:Colonic Neoplasms / Q000139:chemically induced* / Q000378:metabolism; D003959:Diamines / Q000494:pharmacology*; D008297:Male; D009955:Ornithine Decarboxylase / Q000378:metabolism*; D065108:Ornithine Decarboxylase Inhibitors; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*
D003959:Diamines; D065108:Ornithine Decarboxylase Inhibitors; D014660:Vasoactive Intestinal Peptide; C009475:trimethylenediamine; D009955:Ornithine Decarboxylase; D001397:Azoxymethane