α-Difluoromethylornithine inhibits cell growth stimulated by a tumor-promoting rat urinary fraction
Homma, Yukio; Ozono, Seiichiro; Numata, Isao; Seidenfeld, Jerome; Oyasu, Ryoichi; Homma Yukio; Departments of Pathology, Northwestern University Medical School and Cancer Center; Ozono Seiichiro; Departments of Pathology, Northwestern University Medical School and Cancer Center; Numata Isao; Departments of Pathology, Northwestern University Medical School and Cancer Center; Department of Urology, Tohoku University School of Medicine; Seidenfeld Jerome; Pharmacology, Northwestern University Medical School and Cancer Center; Oyasu Ryoichi; Departments of Pathology, Northwestern University Medical School and Cancer Center
Журнал:
Carcinogenesis
Дата:
1985
Аннотация:
The growth stimulating activity of a tumor-promoting rat urinary fraction (Fraction I), and its inhibition by α-difluoromethylomithine (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 omithine 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.
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