Hepburn P A, Tisdale M J
Pharmaceutical Sciences Institute, Aston University, Birmingham, U.K.
Biochem Pharmacol. 1991 Feb 1;41(3):339-43. doi: 10.1016/0006-2952(91)90529-e.
Transfection of a murine colon adenocarcinoma cell line (MAC13) with DNA extracted from GM892 or Raji cells previously treated with either the methyl- (temozolomide) or ethyl-(CCRG82019) imidazotetrazinones caused a dose-related suppression of cell growth. The effect was proportional to the concentration of DNA transfected and the time of incubation of the donor cell lines with the drugs. It was not shown with X-irradiated DNA suggesting that the effect did not arise from non-specific damage to the DNA. Transfection of MAC13 cells with DNA extracted from GM892 cells was more effective in inhibiting growth than DNA from Raji cells, and temozolomide treated cellular DNA was a more potent growth inhibitor than that from CCRG 82019 treated cells. For both agents the growth inhibitory effect was most marked with DNA extracted 6 hr after drug addition and thereafter the effect decreased up to 24 hr after drug addition. This suggests that the growth inhibitory effect is due to a repairable lesion, and that the terminal mechanism of action of these agents involves targets after DNA.
用先前用甲基（替莫唑胺）或乙基（CCRG82019）咪唑并四嗪酮处理过的GM892或Raji细胞提取的DNA转染小鼠结肠腺癌细胞系（MAC13），会导致细胞生长出现剂量相关的抑制。这种效应与转染的DNA浓度以及供体细胞系与药物孵育的时间成正比。用X射线照射的DNA未显示出这种效应，这表明该效应并非由DNA的非特异性损伤引起。用GM892细胞提取的DNA转染MAC13细胞比用Raji细胞的DNA更有效地抑制生长，并且替莫唑胺处理的细胞DNA比CCRG 82019处理的细胞的DNA是更有效的生长抑制剂。对于这两种药物，在添加药物后6小时提取的DNA的生长抑制作用最为明显，此后直至添加药物后24小时，该效应逐渐减弱。这表明生长抑制效应是由于可修复的损伤，并且这些药物的最终作用机制涉及DNA之后的靶点。
