Courdi A, Milano G, Bouclier M, Lalanne C M
Int J Cancer. 1986 Jul 15;38(1):103-7. doi: 10.1002/ijc.2910380117.
The effect of polyamine depletion on the radiosensitivity of a human tumor cell line was investigated. CAL 18 A cells, derived from a breast carcinoma, were incubated with alpha-difluoromethylornithine (DFMO)--a specific and irreversible inhibitor of ornithine decarboxylase (ODC)--at a 1 mM or 10-mM concentration for either 1 hr or 24 hr and irradiated thereafter. Survival curves of exponentially growing cells revealed a moderate but significant enhancement of radiosensitivity as compared to untreated irradiated cells. Maximum radiosensitization was observed at a concentration of 10 mM after 1 hr incubation. Plateau-phase cells were used to study the effect of polyamine inhibition on repair of radiation-induced potentially lethal damage (PLD). DFMO enhanced the radiation response and significantly inhibited PLD repair in these cells. Measurement of ODC indicated that this enzyme was markedly inactivated upon brief incubation of CAL 18 A cells with DFMO, reflecting a depletion of polyamine synthesis. These results extend findings that have demonstrated enhancement of drug-induced cytotoxicity, and raise the possibility of clinical use of this substance for potentiation of radiation response.
研究了多胺耗竭对人肿瘤细胞系放射敏感性的影响。将源自乳腺癌的CAL 18 A细胞与α-二氟甲基鸟氨酸（DFMO）——鸟氨酸脱羧酶（ODC）的一种特异性不可逆抑制剂——以1 mM或10 mM的浓度孵育1小时或24小时，然后进行辐照。指数生长细胞的存活曲线显示，与未处理的辐照细胞相比，放射敏感性有适度但显著的增强。孵育1小时后，在10 mM的浓度下观察到最大放射增敏作用。平台期细胞用于研究多胺抑制对辐射诱导的潜在致死性损伤（PLD）修复的影响。DFMO增强了这些细胞的辐射反应并显著抑制了PLD修复。ODC的测量表明，在用DFMO短暂孵育CAL 18 A细胞后，该酶明显失活，这反映了多胺合成的耗竭。这些结果扩展了已证明药物诱导的细胞毒性增强的研究结果，并提高了该物质在临床上用于增强辐射反应的可能性。
