Glover T W, Berger C, Coyle J, Echo B
Hum Genet. 1984;67(2):136-42. doi: 10.1007/BF00272988.
Aphidicolin, a specific inhibitor of DNA polymerase alpha, is known to induce chromosomal aberrations. At concentrations that did not greatly affect mitotic index, aphidicolin induced a striking number of chromosome gaps and breaks distributed in a highly nonrandom manner in cultured human lymphocytes. Specific chromosome bands, especially 2q31, 3p14, 6q26, 7q32, 16q23, and Xp22 were preferentially damaged in lymphocytes from each of 12 subjects studied. Total and site-specific damage was dose dependent and greatly increased when folic acid was removed from the medium. The sites most sensitive to aphidicolin damage include the "hot spots" seen under conditions of thymidylate stress and in studies of spontaneous chromosomal damage. The fragile X site, which can also be induced by thymidylate stress, was not induced by aphidicolin in lymphocytes, suggesting a separate mechanism for its induction. Aphidicolin represents a novel tool for detection of hot spots on human chromosomes through the mechanism of DNA polymerase alpha inhibition. The hot spots induced by aphidicolin represent a new class of fragile sites which we term common fragile sites.
阿非迪霉素是DNA聚合酶α的一种特异性抑制剂，已知其可诱导染色体畸变。在对有丝分裂指数影响不大的浓度下，阿非迪霉素在培养的人淋巴细胞中诱导出大量染色体间隙和断裂，且分布高度非随机。在研究的12名受试者的淋巴细胞中，特定的染色体带，尤其是2q31、3p14、6q26、7q32、16q23和Xp22优先受损。总的和位点特异性损伤呈剂量依赖性，当培养基中去除叶酸时，损伤大大增加。对阿非迪霉素损伤最敏感的位点包括在胸苷酸应激条件下和自发染色体损伤研究中所见的“热点”。脆性X位点也可由胸苷酸应激诱导，但在淋巴细胞中阿非迪霉素不会诱导该位点，这表明其诱导机制不同。阿非迪霉素是通过抑制DNA聚合酶α的机制来检测人类染色体上热点的一种新工具。阿非迪霉素诱导的热点代表一类新的脆性位点，我们称之为常见脆性位点。
