Martelli A, Mattioli F, Pastorino G, Robbiano L, Allavena A, Brambilla G
Institute of Pharmacology, University of Genoa, Italy.
Mutat Res. 1991 May;260(1):65-72. doi: 10.1016/0165-1218(91)90081-v.
The results of this work, carried out to extend the limited information at present available on the genotoxic potential of chloramphenicol (CAP), indicate that in millimolar concentrations this antibacterial agent produced a minimal amount of DNA fragmentation in both V79 cells and metabolically competent rat hepatocytes. Moreover, a level of DNA-repair synthesis indicative of a weak but positive response was detected in primary cultures of liver cells obtained from 2 of 3 human donors, and a borderline degree of repair was present in those prepared from rats. The promutagenic character of CAP-induced DNA lesions was confirmed by a low but significant increase in the frequency of 6-thioguanine-resistant clones of V79 cells, which, however, was absent when the exposure was done in the presence of co-cultured rat hepatocytes. Finally, oral administration to rats of 1/2 LD50 CAP did not increase the incidence of either micronucleated polychromatic erythrocytes or micronucleated hepatocytes. Taken as a whole these findings suggest that CAP should be considered a compound intrinsically capable of producing a very weak genotoxic effect, but only at concentrations about 25 times higher than those occurring in patients treated with maximal therapeutic dosages.
开展本研究的目的是扩展目前关于氯霉素（CAP）遗传毒性潜力的有限信息，其结果表明，在毫摩尔浓度下，这种抗菌剂在V79细胞和具有代谢活性的大鼠肝细胞中均产生了极少量的DNA片段化。此外，在来自3名人类供体中2名的肝细胞原代培养物中检测到了一定水平的DNA修复合成，表明有微弱但阳性的反应，而在大鼠制备的肝细胞中存在临界程度的修复。V79细胞对6-硫鸟嘌呤耐药克隆频率虽低但有显著增加，证实了CAP诱导的DNA损伤的前诱变特性，然而，当在共培养的大鼠肝细胞存在的情况下进行暴露时，这种增加并不存在。最后，给大鼠口服1/2 LD50的CAP并没有增加微核多染红细胞或微核肝细胞的发生率。总体而言，这些发现表明，CAP应被视为一种本质上能够产生非常微弱遗传毒性作用的化合物，但仅在浓度比接受最大治疗剂量的患者体内浓度高约25倍时才会如此。
