alpha-Difluoromethylornithine inhibits cell growth stimulated by a tumor-promoting rat urinary fraction. 1985

Y Homma, and S Ozono, and I Numata, and J Seidenfeld, and R Oyasu

The growth stimulating activity of a tumor-promoting rat urinary fraction (Fraction I), and its inhibition by alpha-difluoromethylornithine (DFMO) were examined in vitro using a rat bladder carcinoma cell line, 804G cells. Cell growth was markedly stimulated by Fraction I when added to the basic medium containing 0.2% fetal calf serum (FCS). The increased proliferative activity was associated with an increase in ornithine decarboxylase (ODC) activity and intracellular polyamine content. DFMO effectively inhibited the growth of 804G cells stimulated by Fraction I or by 10% FCS, and the inhibition was associated with suppression of ODC activity and partial depletion of intracellular putrescine and spermidine. Growth inhibition was reversed by exogenous putrescine. These results show that (i) urinary Fraction I, both a tumor promoter in bladder carcinogenesis and an ODC inducer in 804G cells, has potent mitogenicity in 804G cells, and (ii) the mitogenicity is inhibited by DMFO, an irreversible inhibitor of ODC.

UI MeSH Term Description Entries
D009952 Ornithine An amino acid produced in the urea cycle by the splitting off of urea from arginine. 2,5-Diaminopentanoic Acid,Ornithine Dihydrochloride, (L)-Isomer,Ornithine Hydrochloride, (D)-Isomer,Ornithine Hydrochloride, (DL)-Isomer,Ornithine Hydrochloride, (L)-Isomer,Ornithine Monoacetate, (L)-Isomer,Ornithine Monohydrobromide, (L)-Isomer,Ornithine Monohydrochloride, (D)-Isomer,Ornithine Monohydrochloride, (DL)-Isomer,Ornithine Phosphate (1:1), (L)-Isomer,Ornithine Sulfate (1:1), (L)-Isomer,Ornithine, (D)-Isomer,Ornithine, (DL)-Isomer,Ornithine, (L)-Isomer,2,5 Diaminopentanoic Acid
D009955 Ornithine Decarboxylase A pyridoxal-phosphate protein, believed to be the rate-limiting compound in the biosynthesis of polyamines. It catalyzes the decarboxylation of ornithine to form putrescine, which is then linked to a propylamine moiety of decarboxylated S-adenosylmethionine to form spermidine. Ornithine Carboxy-lyase,Carboxy-lyase, Ornithine,Decarboxylase, Ornithine,Ornithine Carboxy lyase
D011073 Polyamines Amine compounds that consist of carbon chains or rings containing two or more primary amino groups. Polyamine
D001749 Urinary Bladder Neoplasms Tumors or cancer of the URINARY BLADDER. Bladder Cancer,Bladder Neoplasms,Cancer of Bladder,Bladder Tumors,Cancer of the Bladder,Malignant Tumor of Urinary Bladder,Neoplasms, Bladder,Urinary Bladder Cancer,Bladder Cancers,Bladder Neoplasm,Bladder Tumor,Cancer, Bladder,Cancer, Urinary Bladder,Neoplasm, Bladder,Neoplasm, Urinary Bladder,Tumor, Bladder,Tumors, Bladder,Urinary Bladder Neoplasm
D002273 Carcinogens Substances that increase the risk of NEOPLASMS in humans or animals. Both genotoxic chemicals, which affect DNA directly, and nongenotoxic chemicals, which induce neoplasms by other mechanism, are included. Carcinogen,Oncogen,Oncogens,Tumor Initiator,Tumor Initiators,Tumor Promoter,Tumor Promoters,Initiator, Tumor,Initiators, Tumor,Promoter, Tumor,Promoters, Tumor
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D004273 DNA, Neoplasm DNA present in neoplastic tissue. Neoplasm DNA
D000518 Eflornithine An inhibitor of ORNITHINE DECARBOXYLASE, the rate limiting enzyme of the polyamine biosynthetic pathway. Difluoromethylornithine,alpha-Difluoromethylornithine,DL-alpha-Difluoromethylornithine,Eflornithine Hydrochloride,Eflornithine Monohydrochloride, Monohydrate,MDL-71,782 A,Ornidyl,RMI 71782,Vaniqa,alpha-Difluoromethyl Ornithine,DL alpha Difluoromethylornithine,MDL 71,782 A,MDL71,782 A,Ornithine, alpha-Difluoromethyl,alpha Difluoromethyl Ornithine,alpha Difluoromethylornithine
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D014556 Urine Liquid by-product of excretion produced in the kidneys, temporarily stored in the bladder until discharge through the URETHRA.

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