Agarwal R P, Busso M E, Mian A M, Resnick L
Department of Oncology, University of Miami School of Medicine, FL 33101.
AIDS Res Hum Retroviruses. 1989 Oct;5(5):541-50. doi: 10.1089/aid.1989.5.541.
The uptake of 2',3'-dideoxyadenosine was examined in a human immunodeficiency virus (HIV) infected and uninfected T cell line (H9 cells), a B cell line (Namalwa), and in normal peripheral blood mononuclear cells. After a 10-minute incubation at ambient temperature, the intracellular 2',3'-dideoxyadenosine-derived radioactivity was 8- to 16-fold higher than the extracellular radioactivity. In metabolically inactive cells (0 degrees C), the intracellular and extracellular 2',3'-dideoxyadenosine-derived radioactivities were nearly equal. In infected and noninfected H9 cells, a large excess of p-nitrobenzylmercaptopurine riboside or pyrimidine nucleosides weakly inhibited the uptake of 2',3'-dideoxyadenosine (7-30%), whereas deoxycoformycin was a stronger inhibitor (50-80%). Purine nucleosides minimally enhanced the uptake (10-20%). The cellular uptake was not associated with the accumulation of dideoxyadenosine triphosphate. In normal peripheral blood mononuclear cells, the uptake of 2',3'-dideoxyadenosine was inhibited by all agents except 2'-deoxyadenosine (15% enhancement). In contrast to H9 cells, the formation and accumulation of dideoxyadenosine triphosphate paralleled the uptake of dideoxyadenosine. The results of these studies suggest that the major route of transport of 2',3'-dideoxyadenosine into cells is by simple diffusion and that different metabolic patterns exist among cell lines and normal peripheral blood mononuclear cells. An understanding of these cellular differences could aid in the development of therapeutic strategies directed against HIV.
在人免疫缺陷病毒（HIV）感染和未感染的T细胞系（H9细胞）、B细胞系（Namalwa）以及正常外周血单核细胞中检测了2',3'-二脱氧腺苷的摄取情况。在室温下孵育10分钟后，细胞内2',3'-二脱氧腺苷衍生的放射性比细胞外放射性高8至16倍。在代谢不活跃的细胞（0℃）中，细胞内和细胞外2',3'-二脱氧腺苷衍生的放射性几乎相等。在感染和未感染的H9细胞中，大量过量的对硝基苄基巯基嘌呤核苷或嘧啶核苷对2',3'-二脱氧腺苷的摄取有微弱抑制作用（7 - 30%），而脱氧助间型霉素是更强的抑制剂（50 - 80%）。嘌呤核苷对摄取的增强作用最小（10 - 20%）。细胞摄取与三磷酸二脱氧腺苷的积累无关。在正常外周血单核细胞中，除2'-脱氧腺苷（增强15%）外，所有试剂均抑制2',3'-二脱氧腺苷的摄取。与H9细胞相反，三磷酸二脱氧腺苷的形成和积累与二脱氧腺苷的摄取平行。这些研究结果表明，2',3'-二脱氧腺苷进入细胞的主要运输途径是简单扩散，并且不同细胞系和正常外周血单核细胞之间存在不同的代谢模式。了解这些细胞差异有助于制定针对HIV的治疗策略。
