Programa de Pós-Graduação em Diagnóstico Genético e Molecular, Universidade Luterana do Brazil, Canoas, RS Brazil.
Genet Mol Biol. 2010 Oct;33(4):756-60. doi: 10.1590/S1415-47572010005000084. Epub 2010 Dec 1.
This study evaluated the clastogenic and/or aneugenic potential of three nucleoside reverse transcriptase inhibitors (zidovudine - AZT, lamivudine - 3TC and stavudine - d4T) using the cytokinesis-block micronucleus (CBMN) assay in human lymphocyte cultures. All three inhibitors produced a positive response when tested in binucleated cells. The genotoxicity of AZT and 3TC was restricted to binucleated cells since there was no significant increase in the frequency of micronuclei in mononucleated cells. This finding indicated that AZT and 3TC caused chromosomal breakage and that their genotoxicity was related to a clastogenic action. In addition to the positive response observed with d4T in binucleated cells, this drug also increased the frequency of micronuclei in mononucleated cells, indicating clastogenic and aneugenic actions. Since the structural differences between AZT and 3TC and AZT and d4T involve the 3' position in the 2'-deoxyribonucleoside and in an unsaturated 2',3',dideoxyribose, respectively, we suggest that an unsaturated 2', 3', dideoxyribose is responsible for the clastogenic and aneugenic actions of d4T.
本研究采用胞质分裂阻滞微核（CBMN）试验评估了三种核苷逆转录酶抑制剂（齐多夫定 - AZT、拉米夫定 - 3TC 和司他夫定 - d4T）的致裂和/或非整倍体形成潜能。在双核细胞中，这三种抑制剂均产生阳性反应。AZT 和 3TC 的遗传毒性仅限于双核细胞，因为单核细胞中微核的频率没有显著增加。这一发现表明 AZT 和 3TC 导致染色体断裂，其遗传毒性与致裂作用有关。除了在双核细胞中观察到 d4T 的阳性反应外，该药物还增加了单核细胞中微核的频率，表明具有致裂和非整倍体形成作用。由于 AZT 和 3TC 与 AZT 和 d4T 之间的结构差异分别涉及 2'-脱氧核糖核苷的 3'位和不饱和的 2'、3'、二脱氧核糖，因此我们认为不饱和的 2'、3'、二脱氧核糖是 d4T 的致裂和非整倍体形成作用的原因。
