Maddox A M, Orengo I, Haddox M K
Chemotherapy. 1987;33(2):110-22. doi: 10.1159/000238483.
Difluoromethylornithine (DFMO) is a nonreversible inhibitor of ornithine decarboxylase (ODC), the initial rate-limiting enzyme in the polyamine biosynthetic pathway. When HL60 leukemic cells were incubated in the presence of concentrations of DFMO from 0.05 mM to 5 mM, there was a concentration-dependent inhibition of ODC activity apparent within 24 h. Likewise, cellular polyamine levels were reduced by the presence of DFMO in a concentration-dependent manner after 4 days. The growth of cells incubated with 0.5 mM or greater was inhibited after 3-4 cell doublings. When the concentration of DFMO was less than 0.5 mM, growth was not inhibited. Methylglyoxal-bis(guanylhydrazone) (MGBG) uptake was enhanced in cells treated with concentrations of 0.05-0.5 mM DFMO, but not enhanced in cells treated with DFMO concentrations of 1 mM or greater. DFMO-induced cellular polyamine depletion does enhance MGBG uptake into HL60 cells, but treatment with high concentrations of DFMO, which deplete polyamines to the extent that growth is inhibited, negate this effect.
二氟甲基鸟氨酸（DFMO）是鸟氨酸脱羧酶（ODC）的不可逆抑制剂，ODC是多胺生物合成途径中的初始限速酶。当HL60白血病细胞在浓度为0.05 mM至5 mM的DFMO存在下孵育时，24小时内ODC活性出现浓度依赖性抑制。同样，4天后，DFMO的存在使细胞多胺水平以浓度依赖性方式降低。在3 - 4次细胞倍增后，用0.5 mM或更高浓度DFMO孵育的细胞生长受到抑制。当DFMO浓度低于0.5 mM时，生长未受抑制。在用浓度为0.05 - 0.5 mM的DFMO处理的细胞中，甲基乙二醛双（脒腙）（MGBG）摄取增强，但在用1 mM或更高浓度DFMO处理的细胞中未增强。DFMO诱导的细胞多胺耗竭确实会增强MGBG对HL60细胞的摄取，但用高浓度DFMO处理会使多胺耗竭至生长受到抑制的程度，从而抵消这种作用。
