Dietary polyamines promote the growth of azoxymethane-induced aberrant crypt foci in rat colon.
We have examined whether dietary polyamines influence the formation and initial growth of azoxymethane (AOM)-induced aberrant crypt foci (ACF) in rat colon. Effects of a combination of dietary polyamines at three dose levels (putrescine: 50, 280, 740 nmol/g; spermidine: 10, 261, 763 nmol/g; spermine: 1, 31, 91 nmol/g) in the polyamine-poor AIN-76A diet were studied in animals in two different experimental situations: animals treated with AOM alone and animals treated with AOM + difluoromethylornithine (DFMO), a specific inhibitor of endogenous polyamine synthesis. In both experimental situations, dietary polyamines enhanced the growth of ACF, expressed as the number of large ACF (foci with three or more aberrant crypts, ACF > or = 3), whereas the formation of ACF, expressed as the number of ACF, was apparently not altered. In animals treated with AOM alone, maximal growth enhancing effect on ACF was nearly obtained with the median level of dietary polyamine. In rats fed a low polyamine diet, basic AIN-76A, DFMO reduced the growth of AOM-induced ACF by 83%. This inhibitory effect of DFMO was counteracted by dietary polyamines in a dose-dependent manner, and it was abolished at the highest level of polyamines. In conclusion, it was demonstrated that dietary polyamines are able to enhance the growth of AOM-induced ACF. Further, dietary polyamines reversed the DFMO-caused inhibition of ACF growth, probably by compensating for the DFMO-reduced endogenous polyamine synthesis.
Paulsen
J E
JE
Department of Environmental Medicine, National Institute of Public Health, Oslo, Norway.
Reistad
R
R
Eliassen
K A
KA
Sjaastad
O V
OV
Alexander
J
J
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001397:Azoxymethane; D002273:Carcinogens; D003106:Colon / Q000187:drug effects* / Q000378:metabolism; D004357:Drug Synergism; D000518:Eflornithine / Q000494:pharmacology*; D006128:Growth / Q000187:drug effects; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism; D007421:Intestine, Small / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009955:Ornithine Decarboxylase / Q000378:metabolism; D011073:Polyamines / Q000008:administration & dosage / Q000009:adverse effects* / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344
D000970:Antineoplastic Agents; D002273:Carcinogens; D011073:Polyamines; D009955:Ornithine Decarboxylase; D001397:Azoxymethane; D000518:Eflornithine