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Microbial flora in the gastrointestinal tract abolishes cytostatic effects of α‐difluoromethylornithine in vivo
Author(s) -
Hessels J.,
Kingma A. W.,
Ferwerda H.,
Keu J.,
Van Den Berg G. A.,
Muskiet F. A. J.
Publication year - 1989
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910430632
Subject(s) - putrescine , spermidine , polyamine , spermine , ornithine decarboxylase , in vivo , biology , biochemistry , gastrointestinal tract , pharmacology , in vitro , enzyme , microbiology and biotechnology
Although treatment with the ornithine decarboxylase inhibitor α‐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 Gl tract. We studied selectively (aerobic) and totally (aerobic + anaerobic) Gl tract‐decontaminated L1210‐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 G 0 ,/G 1 , 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.