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

✍ Scribed by J. Hessels; A. W. Kingma; H. Ferwerda; J. Keu; G. A. Van Den Berg; F. A. J. Muskiet

• Publisher: John Wiley and Sons
• Year: 1989
• Tongue: French
• Weight: 868 KB
• Volume: 43
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/ijc.2910430632

✦ Synopsis

Although treatment with the ornithine decarboxylase inhibitor a-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 LI 2 IObearing mice fed with 3 types of diet differing in their polyamine and carbohydrate residue contents and treated with combinations of intraperitoneal DFMO and oral deuteriumlabelled 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 LI 21 0 cells accumulate in the GdG, phase of the cell cycle. Although orally administered deuterium-labelled putrescine gave rise to deuterium labelling of LIZ10 putrescine, spermidine and spermine, the polyamine levels in our diets played only a minor role.