Lialiaris Theodore, Lyratzopoulos Emmanuel, Papachristou Fotini, Simopoulou Maria, Mourelatos Constantinos, Nikolettos Nikolaos
Department of Genetics, Medical School, Demokritus University of Thrace, Alexandroupolis 68100, Greece.
Mutagenesis. 2008 Sep;23(5):347-54. doi: 10.1093/mutage/gen020. Epub 2008 May 22.
Melatonin (MLT) is a natural oncostatic factor of the human body as well as an antioxidant thus protects the nuclear DNA from oxidative damage. It also has the ability to reduce the side effects of various drugs when used as a combination therapy. The anti-neoplastic agent melphalan (MEL), which encompasses a number of side effects, is a strong alkylating agent and a potent inducer of sister chromatid exchanges (SCEs). The aim of the current in vitro study was to investigate the ability of MLT to reduce the genotoxic effect of MEL on normal human cultured peripheral lymphocytes. Cells were treated with both agents at various concentrations (MLT 100, 200 and 400 microM and MEL 330, 490 and 650 nM) and incubated for 72 h prior harvesting. The levels of cytostaticity, cytotoxicity and genotoxicity were qualitatively evaluated using the proliferation rate index, the mitotic index and the SCE methodology, respectively. Our results demonstrated the protective effect of MLT on cells treated with MEL in vitro. The greatest protective effect of MLT at 100 and 400 microM was illustrated against 330 nM of MEL in comparison with all other doses of MEL. These observations imply that MLT may be proved useful in reducing some of the toxic effects associated with certain classes of chemotherapeutic agents and other chemical and physical mutagens and carcinogens, acting both as an antioxidant-radical scavenger and a protective mechanism against cellular damage due to exposure to free radical-producing agents. It is essential to investigate substances with protective properties which are normally produced from the human body.
褪黑素（MLT）是人体的一种天然抑癌因子，也是一种抗氧化剂，可保护核DNA免受氧化损伤。当作为联合疗法使用时，它还具有减轻各种药物副作用的能力。抗肿瘤药物美法仑（MEL）有多种副作用，是一种强烷化剂和姐妹染色单体交换（SCE）的有效诱导剂。当前这项体外研究的目的是探究MLT降低MEL对正常人类培养外周淋巴细胞的遗传毒性作用的能力。用不同浓度的两种药物（MLT 100、200和400微摩尔/升，MEL 330、490和650纳摩尔/升）处理细胞，并在收获前孵育72小时。分别使用增殖率指数、有丝分裂指数和SCE方法对细胞生长抑制、细胞毒性和遗传毒性水平进行定性评估。我们的结果证明了MLT在体外对用MEL处理的细胞具有保护作用。与所有其他剂量的MEL相比，MLT在100和400微摩尔/升时对330纳摩尔/升的MEL表现出最大的保护作用。这些观察结果表明，MLT可能被证明有助于减轻与某些类别的化疗药物以及其他化学和物理诱变剂及致癌物相关的一些毒性作用，它既作为抗氧化自由基清除剂，又作为一种针对因接触产生自由基的物质而导致细胞损伤的保护机制。研究人体正常产生的具有保护特性的物质至关重要。
