Micronuclei, nucleoplasmic bridges and nuclear buds induced in folic acid deficient human lymphocytes - evidence for breakage-fusion-bridge cycles in the cytokinesis-block micronucleus assay

Micronuclei, nucleoplasmic bridges and nuclear buds induced in folic acid deficient human lymphocytes - evidence for breakage-fusion-bridge cycles in the cytokinesis-block micronucleus assay
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DOI:
10.1016/s0027-5107(02)00086-6
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发表时间:
2002-07-25
影响因子:
2.3
通讯作者:
Crott, JW
Crott, JW
中科院分区:
医学4区
文献类型:
--
作者:
Fenech, M;Crott, JW

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我们已经验证了核质桥(NPB)和核芽作为长期淋巴细胞培养物中微核阻断试验中基因组不稳定性生物标志物的分析。将来自20名受试者的淋巴细胞在含有12-120 nM叶酸的培养基中培养9天。在存在胞质分裂抑制剂细胞松弛素-B的情况下孵育24 h后,在第9天对双核细胞的微核(MN)、NPB和核出芽进行评分。叶酸浓度与上述染色体损伤指标均呈极显著相关(P < 0.0001)和负相关(r = -0.63 ~-0.74)。60-120 nM叶酸可将染色体损伤降至最低,该浓度高于血浆中正常观察到的叶酸浓度(
We have validated the analysis of nucleoplasmic bridges (NPBs) and nuclear buds as biomarkers of genomic instability within the cytokinesis-block micronucleus assay in long-term lymphocyte cultures. Lymphocytes from 20 subjects were cultured in medium containing 12-120 nM folic acid for 9 days. Binucleate cells were scored for micronuclei (MN), NPBs and nuclear budding on day nine after 24 h incubation in the presence of the cytokinesis inhibitor cytochalasin-B. Folic acid concentration was correlated significantly (P < 0.0001) and negatively (r = -0.63 to -0.74) with all these markers of chromosome damage. Chromosome damage was minimised at 60-120 nM folic acid, which is greater than the concentration of folate normally observed in plasma (