Minchin R F, Martin R L, Ilett K F
Department of Pharmacology, University of Western Australia, Nedlands.
Life Sci. 1989;45(1):63-9. doi: 10.1016/0024-3205(89)90436-0.
We have examined the effect of difluoromethylornithine on the ability of B16 melanoma cells to take up putrescine and the 4,4'-dipyridyl herbicide paraquat. Pretreatment with difluoromethylornithine for 24 hr enhanced putrescine uptake by inducing the maximum capacity of the transport system without affecting the Km for the substrate. Paraquat uptake was minor compared with that of putrescine and was not affected by difluoromethylornithine. Neither putrescine, spermidine or spermine at concentrations up to 100 microM inhibited the accumulation of paraquat. However, paraquat competitively inhibited putrescine transport (Ki = 54 +/- 10 microM). Exposure of the B16 melanoma cells for 24 hr to increasing concentrations of paraquat produced a dose-dependent inhibition of DNA synthesis. Difluoromethylornithine pretreatment did not affect paraquat toxicity. These data show that paraquat is not taken up into B16 melanoma cells by the uptake system responsible for transporting putrescine. Moreover, it is likely that the difluoromethylornithine inducible polyamine transport system in B16 melanoma cells is characteristically different to that previously described in normal mammalian lung since the latter is reportedly capable of transporting both putrescine and paraquat.
我们研究了二氟甲基鸟氨酸对B16黑色素瘤细胞摄取腐胺和4,4'-联吡啶除草剂百草枯能力的影响。用二氟甲基鸟氨酸预处理24小时可通过诱导转运系统的最大容量来增强腐胺摄取,而不影响底物的米氏常数(Km)。与腐胺相比,百草枯的摄取量较少,且不受二氟甲基鸟氨酸的影响。浓度高达100微摩尔的腐胺、亚精胺或精胺均未抑制百草枯的积累。然而,百草枯竞争性抑制腐胺转运(抑制常数Ki = 54 ± 10微摩尔)。将B16黑色素瘤细胞暴露于浓度不断增加的百草枯中24小时,会产生剂量依赖性的DNA合成抑制。二氟甲基鸟氨酸预处理不影响百草枯的毒性。这些数据表明,百草枯不是通过负责转运腐胺的摄取系统进入B16黑色素瘤细胞的。此外,B16黑色素瘤细胞中二氟甲基鸟氨酸诱导的多胺转运系统可能与先前在正常哺乳动物肺中描述的系统有显著差异,因为据报道后者能够转运腐胺和百草枯。