Lehmann Mauricio, Franco Aline, de Souza Prudente Vilar Knulp, Luķza Reguly Maria, de Andrade Heloísa Helena Rodrigues
Departamento de Genética, Universidade Federal do Rio Grande do Sul, CP 15053, 91501-970, Porto Alegre, RS, Brazil.
Mutat Res. 2003 Aug 5;539(1-2):167-75. doi: 10.1016/s1383-5718(03)00162-1.
The genotoxic effects of the anthracycline doxorubicin (DOX) and two of its analogues, epirubicin (EPI) and pirarubicin (THP) were studied using the wing Somatic Mutation and Recombination Test (SMART) in Drosophila melanogaster. These compounds are classified as topoisomerase II (topo II) poisons, acting by stabilizing a topoisomerase II-cleaved DNA complex. Using the standard version of the SMART test it was possible to estimate the quantitative and qualitative genotoxic effects of these compounds, comparing the wing spot frequencies in marker- and balancer-heterozygous flies. The results obtained indicate that all three compounds induce a high frequency of spots related to homologous recombination (HR), which is the major event responsible for their genetic toxicity. Pirarubicin was the most genotoxic anthracycline, inducing approximately 21 times more genetic lesions than doxorubicin, probably due to the presence of a second sugar ring in the amino sugar moiety in its chemical structure. Although the only difference between epirubicin and doxorubicin is the steric position of the amino sugar 4'-OH in the molecule, epirubicin is approximately 1.6 times as genotoxic as doxorubicin.
利用果蝇的翅体细胞突变与重组试验（SMART）研究了蒽环类药物阿霉素（DOX）及其两种类似物表柔比星（EPI）和吡柔比星（THP）的遗传毒性作用。这些化合物被归类为拓扑异构酶II（topo II）毒物，通过稳定拓扑异构酶II切割的DNA复合物发挥作用。使用SMART试验的标准版本，可以通过比较标记杂合子和平衡子杂合子果蝇的翅斑频率，来估计这些化合物的定量和定性遗传毒性作用。所得结果表明，所有三种化合物均诱导与同源重组（HR）相关的高频率斑点，这是其遗传毒性的主要原因。吡柔比星是遗传毒性最强的蒽环类药物，其诱导的遗传损伤比阿霉素多约21倍，这可能是由于其化学结构中氨基糖部分存在第二个糖环。尽管表柔比星和阿霉素之间的唯一区别是分子中氨基糖4'-OH的空间位置，但表柔比星的遗传毒性约为阿霉素的1.6倍。
