Dietary polyamines promote the growth of azoxymethane-induced aberrant crypt foci in rat colon |
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Authors: | Paulsen JE; Reistad R; Eliassen KA; Sjaastad OV; Alexander J |
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Affiliation: | Department of Environmental Medicine, National Institute of Public Health, Oslo, Norway. |
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Abstract: | 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.
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