Ustundag A, Duydu Y
Department of Pharmaceutical Toxicology, Faculty of Pharmacy, University of Ankara, 06100 Tandoğan, Ankara, Turkey.
Biol Trace Elem Res. 2007 Summer;117(1-3):53-64. doi: 10.1007/BF02698083.
As is well known from earlier studies, the genotoxic effect of lead exposure was partly attributed to the formation of the highly reactive oxygen metabolites (ROMs) in the blood. However, lead ions have no ability to generate ROMs. Therefore, the recently published studies paid more attention to the role of delta-aminolevulinic acid (ALA) accumulation in lead-induced DNA damage. If the above-mentioned assumptions were taken into consideration, it seemed a reasonable approach to study the possible protective effects of antioxidants against genotoxic effects of lead. According to our results, N-acetylcysteine (NAC) and melatonin (MEL) were able to reduce significantly (p<0.05) the lead- and ALA-induced sister chromatid exchange frequencies in human lymphocytes in vitro. In spite of a relative reduction in the lead- and ALA-induced micronucleus formation in human lymphocytes, the reduction was not statistically significant (p>0.05). These results could be evaluated as supportive evidence for the hypothesis that increased antioxidant capacity of cells might fortify the efficiency of protective pathways against cytogenetic damage in lead exposure.
正如早期研究所熟知的,铅暴露的遗传毒性作用部分归因于血液中高反应性氧代谢产物(ROMs)的形成。然而,铅离子没有产生ROMs的能力。因此,最近发表的研究更多地关注δ-氨基乙酰丙酸(ALA)积累在铅诱导的DNA损伤中的作用。如果考虑上述假设,研究抗氧化剂对铅遗传毒性作用的可能保护作用似乎是一种合理的方法。根据我们的结果,N-乙酰半胱氨酸(NAC)和褪黑素(MEL)能够显著降低(p<0.05)体外培养的人淋巴细胞中铅和ALA诱导的姐妹染色单体交换频率。尽管铅和ALA诱导的人淋巴细胞微核形成有相对减少,但这种减少没有统计学意义(p>0.05)。这些结果可被视为支持以下假设的证据:细胞抗氧化能力的增强可能会加强铅暴露时针对细胞遗传损伤的保护途径的效率。