Rossi L, Brandi G, Schiavano G F, Chiarantini L, Albano A, Magnani M
Istituto di Chimica Biologica G. Fornaini, Università degli Studi 61029, Urbino, Italy.
Chem Biol Interact. 1992 Dec;85(2-3):255-63. doi: 10.1016/0009-2797(92)90066-t.
3T3 mouse embryo fibroblast cell growth was inhibited in a concentration dependent manner by 2',3'-dideoxycytidine (ddCyd), a strong inhibitor of human immunodeficiency virus. Cell growth inhibition was associated with an increased incorporation of ddCyd into cell DNA. In contrast SP2/0-Ag14 (a mouse myeloma) cell growth is not inhibited by 100 microM ddCyd both in the presence or absence of hypoxanthine and thymidine. Furthermore, in vitro spleen cell proliferation, upon phytohemagglutinin (PHA) addition, was much more affected by ddCyd in C57BL/6 mice than in Swiss albino mice. That indeed ddCyd affects spleen cell proliferation was confirmed by studies on splenocytes obtained from C57BL/6 mice that received ddCyd for 2 weeks in drinking water. These results suggest that ddCyd toxicity in mice is cell and strain dependent and that the toxicity mechanism is related to the incorporation of the drug in cell DNA.
人免疫缺陷病毒的强效抑制剂2',3'-双脱氧胞苷（ddCyd）以浓度依赖的方式抑制3T3小鼠胚胎成纤维细胞的生长。细胞生长抑制与ddCyd掺入细胞DNA的增加有关。相比之下，无论有无次黄嘌呤和胸腺嘧啶，100微摩尔的ddCyd都不会抑制SP2/0-Ag14（一种小鼠骨髓瘤）细胞的生长。此外，添加植物血凝素（PHA）后，体外脾细胞增殖在C57BL/6小鼠中比在瑞士白化小鼠中受ddCyd的影响更大。通过对从饮用含ddCyd水两周的C57BL/6小鼠获得的脾细胞进行研究，证实了ddCyd确实会影响脾细胞增殖。这些结果表明，ddCyd对小鼠的毒性具有细胞和品系依赖性，且毒性机制与药物掺入细胞DNA有关。
