Microbial flora in the gastrointestinal tract abolishes cytostatic effects of alpha-difluoromethylornithine in vivo.

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.

Effect of dietary fat saturation on survival of mice with L1210 leukemia.

We examined L1210 murine leukemia growth rate and survival of host male DBA/2J mice fed a diet rich in either polyunsaturated fat (16% sunflower oil) or saturated fat (16% coconut oil). The survival of mice that received transplants of L1210 leukemia cells was longer among the animals that had ingested a diet rich in the saturated fat as compared to those fed the more unsaturated fat. In duplicate experiments, the mean survivals of mice fed coconut oil were 200.9 +/- 1.6 and 202.5 +/- 3.4 hours compared to 188.7 +/- 5.3 and 187.6 +/- 3.5 hours for those fed sunflower oil. Tumor growth rate or the rate of DNA synthesis by the leukemia cells did not differ between the two experimental groups. Therefore, the alteration in survival was apparently due to an effect of the diets on the responses of the hosts rather than their effect on tumor size or growth rate.