Although treatment with the ornithine decarboxylase inhibitor alpha-difluoromethylornithine (DFMO) leads to depletion of intracellular polyamines and to related growth inhibition in vitro, its cytostatic effects in vivo are disappointing. This may be due to abolition of DFMO-induced growth inhibition by polyamines released during normal body cell turnover, to dietary polyamines, or to putrescine synthesized by the microbial flora in the GI tract. We studied selectively (aerobic) and totally (aerobic + anaerobic) GI tract-decontaminated LI210-bearing mice fed with 3 types of diet differing in their polyamine and carbohydrate residue contents and treated with combinations of intraperitoneal DFMO and oral deuterium-labelled putrescine. Our data show that, irrespective of diet type, total decontamination markedly potentiates the moderate tumor growth inhibition that is caused by DFMO alone. During total decontamination, growth-inhibited L1210 cells accumulate in the G0/G1 phase of the cell cycle. Although orally administered deuterium-labelled putrescine gave rise to deuterium labelling of L1210 putrescine, spermidine and spermine, the polyamine levels in our diets played only a minor role.
It has been suggested that milk polyamines stimulate GI tract proliferation and maturation in newborns. We determined human milk polyamine concentrations and estimated 24-h outputs on days 16 +/- 4 (n = 98), 44 +/- 3 (n = 97) and 91 +/- 6 (n = 25) after delivery. Median concentrations in micromolars were, respectively, putrescine 0.77, 0.63, and 0.63; spermidine 4.54, 3.07, and 2.73; spermine 3.76, 2.90, and 2.22; and total polyamines 9.82, 6.83, and 5.71. Concentrations of spermidine, spermine, and total polyamines decreased during the observation period. Putrescine, spermidine, and spermine milk/maternal plasma ratios were estimated to be 16-19, 14-24, and 44-75, respectively. It would appear that milk polyamines are derived from the high polyamine contents in the mammary gland and that they may be important in infant nutrition.
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