Heston W D, Kadmon D, Covey D F, Fair W R
Cancer Res. 1984 Mar;44(3):1034-40.
The uptake of exogenously administered radiolabeled polyamines by a rat prostate-derived tumor line, the Dunning R3327 MAT-Lu, and various normal tissues was studied. Pretreatment of tumor cells in vitro with alpha-difluoromethylornithine (DFMO), a polyamine synthesis inhibitor, resulted in a markedly enhanced uptake of both [14C]putrescine and [14 C]spermidine. The in vitro uptake of [14C]putrescine by these cells was effectively inhibited by unlabeled spermine, spermidine, 1,8-diaminooctane, 1,7-diaminoheptane, 1,6-diaminohexane, 1,5-diaminopentane, 1,4-diaminopentane, and 1,4-diaminobutane, but less effectively by 1,4-diamino-2,3-butene and 1,4-diamino-2,3-butyne. The diamines, 1,3-diaminopropane and 1,2-diaminoethane, were ineffective in inhibiting [14C]putrescine uptake in vitro into the R3327 MAT-Lu cell line. When tumor-bearing animals were pretreated with DFMO or with DFMO and 5-alpha-dihydrotestosterone propionate, the tumor and prostate uptake of [14C]putrescine and [14C]-cadaverine was enhanced but not substantially increased in other tissues. In contrast to the in vitro results, spermidine and spermine were not enhanced substantially by DFMO pretreatment into any tissue, and their uptake into the tumor actually decreased. Ethylenediamine, which does not utilize the polyamine transport system, did not have its uptake increased into any tissue following DFMO pretreatment. The chemotherapeutic agent, methylglyoxal bis(guanylhydrazone), which utilizes the polyamine transport system for uptake into cells, exhibited uptake behavior different from that of the polyamines. Thus, methylglyoxal bis(guanylhydrazone) uptake into the tumor was not significantly increased or decreased by DFMO or by DFMO + 5-alpha-dihydrotestosterone propionate pretreatment, and only the ventral, but not the dorsal-lateral, lobe of the prostate showed increased uptake of methylglyoxal bis(guanylhydrazone) following DFMO + 5-alpha-dihydrotestosterone propionate pretreatment.
研究了大鼠前列腺来源的肿瘤细胞系Dunning R3327 MAT-Lu以及各种正常组织对外源性给予的放射性标记多胺的摄取情况。用多胺合成抑制剂α-二氟甲基鸟氨酸（DFMO）对肿瘤细胞进行体外预处理，导致[14C]腐胺和[14C]亚精胺的摄取均显著增强。这些细胞对[14C]腐胺的体外摄取受到未标记的精胺、亚精胺、1,8-二氨基辛烷、1,7-二氨基庚烷、1,6-二氨基己烷、1,5-二氨基戊烷、1,4-二氨基戊烷和1,4-二氨基丁烷的有效抑制，但受到1,4-二氨基-2,3-丁烯和1,4-二氨基-2,3-丁炔的抑制作用较弱。二胺1,3-二氨基丙烷和1,2-二氨基乙烷在体外对R3327 MAT-Lu细胞系摄取[14C]腐胺无效。当荷瘤动物用DFMO或DFMO与丙酸5-α-二氢睾酮进行预处理时，肿瘤和前列腺对[14C]腐胺和[14C]尸胺的摄取增强，但其他组织中摄取并未显著增加。与体外结果相反，DFMO预处理后，亚精胺和精胺在任何组织中的摄取均未显著增强，且它们在肿瘤中的摄取实际上有所下降。不利用多胺转运系统的乙二胺在DFMO预处理后，其在任何组织中的摄取均未增加。利用多胺转运系统进入细胞的化疗药物甲基乙二醛双（胍腙）表现出与多胺不同的摄取行为。因此，DFMO或DFMO + 丙酸5-α-二氢睾酮预处理并未显著增加或降低甲基乙二醛双（胍腙）在肿瘤中的摄取，且仅在DFMO + 丙酸5-α-二氢睾酮预处理后，前列腺腹侧叶而非背外侧叶对甲基乙二醛双（胍腙）的摄取增加。
