Dietary polyamines promote the growth of azoxymethane-induced aberrant crypt foci in rat colon

We have examined whether dietary polyamines influence the formation andinitial growth of azoxymethane (AOM)-induced aberrant crypt foci (ACF) inrat colon. Effects of a combination of dietary polyamines at three doselevels (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 studiedin animals in two different experimental situations: animals treated withAOM alone and animals treated with AOM + difluoromethylornithine (DFMO), aspecific inhibitor of endogenous polyamine synthesis. In both experimentalsituations, dietary polyamines enhanced the growth of ACF, expressed as thenumber of large ACF (foci with three or more aberrant crypts, ACF > or =3), whereas the formation of ACF, expressed as the number of ACF, wasapparently not altered. In animals treated with AOM alone, maximal growthenhancing effect on ACF was nearly obtained with the median level ofdietary polyamine. In rats fed a low polyamine diet, basic AIN-76A, DFMOreduced the growth of AOM-induced ACF by 83%. This inhibitory effect ofDFMO was counteracted by dietary polyamines in a dose- dependent manner,and it was abolished at the highest level of polyamines. In conclusion, itwas demonstrated that dietary polyamines are able to enhance the growth ofAOM-induced ACF. Further, dietary polyamines reversed the DFMO-causedinhibition of ACF growth, probably by compensating for the DFMO-reducedendogenous polyamine synthesis.