Hartmann A, Wess D, Witte I
Universität Oldenburg, Germany.
Mutat Res. 1995 Sep;348(1):7-12. doi: 10.1016/0165-7992(95)90014-4.
Tetracycline (TC) exerts DNA damaging properties which are accelerated in the presence of copper(II). Thereby, reactive oxygen species are generated. We investigated, if copper-accumulating cells show a higher sensitivity to TC compared to normal cells. Fibroblasts with an increased copper content were derived from patients of two genetic disorders, Wilson disease (WD) and Menkes disease (MD). Cytotoxic and genotoxic effects of TC were investigated in different human fibroblasts. The inhibition of cell growth by TC was measured in two normal fibroblast lines, fibroblast lines of two patients with WD and one patient with MD. While TC inhibited cell growth at similar concentrations in normal fibroblasts and the MD fibroblasts, the WD cells were much more sensitive. Furthermore, an increased inhibition of DNA synthesis and an enhanced induction of unscheduled DNA synthesis (UDS) was found in WD cells after a TC-treatment compared to normal cells.
四环素（TC）具有DNA损伤特性，在铜（II）存在的情况下这种损伤会加速。由此会产生活性氧物种。我们研究了与正常细胞相比，积累铜的细胞是否对TC表现出更高的敏感性。铜含量增加的成纤维细胞取自两种遗传性疾病——威尔逊病（WD）和门克斯病（MD）的患者。在不同的人成纤维细胞中研究了TC的细胞毒性和基因毒性作用。在两条正常成纤维细胞系、两名WD患者的成纤维细胞系和一名MD患者的成纤维细胞系中测量了TC对细胞生长的抑制作用。虽然TC在正常成纤维细胞和MD成纤维细胞中以相似浓度抑制细胞生长，但WD细胞更为敏感。此外，与正常细胞相比，TC处理后的WD细胞中DNA合成的抑制增加，且非计划DNA合成（UDS）的诱导增强。
