黄曲霉毒素B1对体外培养的人白细胞拷贝数变异的影响。
Influence of aflatoxin B1 on copy number variants in human leukocytes in vitro.
作者信息
Harutyunyan Tigran, Hovhannisyan Galina, Babayan Nelly, Othman Moneeb Ak, Liehr Thomas, Aroutiounian Rouben
机构信息
Department of Genetics and Cytology, Yerevan State University, 1 Alex Manoogian, 0025 Yerevan, Armenia.
Department of Genetics and Cytology, Yerevan State University, 1 Alex Manoogian, 0025 Yerevan, Armenia ; Institute of Molecular Biology, National Academy of Sciences, 7 Hasratyan, 0014 Yerevan, Armenia.
出版信息
Mol Cytogenet. 2015 Apr 9;8:25. doi: 10.1186/s13039-015-0131-x. eCollection 2015.
BACKGROUND
Aflatoxin B1 (AFB1) is a mycotoxin produced by Aspergillus spec. The latter are worldwide contaminants of food with mutagenic and carcinogenic activities in animals and humans. AFB1 was shown to have deleterious effects on metabolism of eukaryotes in many model systems, including the ability to inhibit DNA replication. An agent that disturbs DNA replication may also have the potential to induce de novo DNA copy number variations (CNVs).
RESULTS
Blood samples of three clinically healthy carriers were treated in vitro with AFB1 and chromosome preparations were subjected to parental origin determination fluorescence in situ hybridization (pod-FISH). Probes able to visualize CNVs in 8p21.2 and 15q11.2 were applied. In this setting here for the first time an influence of AFB1 on molecular-cytogenetically detectable CNVs could be shown.
CONCLUSIONS
The obtained results indicate that: (i) pod-FISH is a single cell directed, sensitive and suitable method for the analysis of mutagen induced CNVs, (ii) AFB1 has the potential to induce in vitro instability of known CNVs in human leukocytes.
背景
黄曲霉毒素B1（AFB1）是由曲霉属真菌产生的一种霉菌毒素。曲霉属真菌是全球范围内的食品污染物，对动物和人类具有致突变和致癌活性。在许多模型系统中，AFB1已被证明对真核生物的代谢具有有害影响，包括抑制DNA复制的能力。一种干扰DNA复制的物质也可能具有诱导新生DNA拷贝数变异（CNV）的潜力。
结果
对三名临床健康携带者的血液样本进行体外AFB1处理，并对染色体标本进行亲本来源确定荧光原位杂交（pod-FISH）。应用能够在8p21.2和15q11.2中可视化CNV的探针。在此情况下，首次证明了AFB1对分子细胞遗传学可检测的CNV有影响。
结论
获得的结果表明：（i）pod-FISH是一种针对单细胞、敏感且适用于分析诱变诱导的CNV的方法，（ii）AFB1有潜力在体外诱导人白细胞中已知CNV的不稳定性。
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