Slamenová D, Dusinská M, Gábelová A, Horváthová E, Oravec C, Chalupa I, Szabová E
Cancer Research Institute, Slovak Academy of Sciences, Bratislava.
Mutat Res. 1994 Oct;322(4):275-85. doi: 10.1016/0165-1218(94)90103-1.
We tested the possible cytotoxic, clastogenic and genotoxic effects of pentoxifylline on different lines of mammalian cells cultured in vitro. This study was part of the developmental research of agapurin, since pentoxifylline represents an effective compound of this drug. Cells treated for a short time manifested a relatively high resistance to the toxic effects of pentoxifylline. Generally, only cells treated for a long time (18 h) or a short time (2 h) with high concentrations of drug manifested sensitivity to the toxic effects of pentoxifylline. Although the tested drug induced DNA synthesis inhibition in V79 and EUE cells and clastogenic effects in V79 cells, it was not able to induce either 6-TGr mutations in the HGPRT locus of V79 cells or morphological transformation of Syrian hamster embryo cells. Adding of microsomal fraction S9 to the treated cells did not markedly change the effects of pentoxifylline on different studied endpoints. We suggest that pentoxifylline has no genotoxic effects, and that the cytotoxicity and induction of chromosomal aberrations were induced by inhibition of cellular DNA replication.
我们测试了己酮可可碱对体外培养的不同系哺乳动物细胞可能产生的细胞毒性、致断裂性和遗传毒性作用。本研究是阿加嘌呤开发研究的一部分，因为己酮可可碱是该药物的一种有效化合物。短期处理的细胞对己酮可可碱的毒性作用表现出相对较高的抗性。一般来说，只有用高浓度药物长期（18小时）或短期（2小时）处理的细胞才对己酮可可碱的毒性作用表现出敏感性。尽管所测试的药物在V79和EUE细胞中诱导了DNA合成抑制，并在V79细胞中产生了致断裂作用，但它既不能诱导V79细胞HGPRT位点的6 - TGr突变，也不能诱导叙利亚仓鼠胚胎细胞的形态转化。向处理过的细胞中添加微粒体组分S9并没有显著改变己酮可可碱对不同研究终点的影响。我们认为己酮可可碱没有遗传毒性作用，其细胞毒性和染色体畸变的诱导是由细胞DNA复制的抑制引起的。
