Saxena Ajit Kumar, Agarwal C S, Kumar Manoj, Srivastava A K, Singh Gajendra
Center of Experimental Medicine & Surgery, Institute of Medical Sciences, Banaras Hindu University, Varanasi-221005, India.
J Exp Ther Oncol. 2007;6(2):175-9.
Chromosomal fragile sites are distributed all over the human genome. Aphidicolin mediated expression frequency of common fragile sites and other chromosomal changes were evaluated in prometaphase/metaphase chromosomes obtained from peripheral blood lymphocytes of colorectal cancer patients. The present study reveals first time high incidence i.e. 6 % of aphidicolin induced chromosome breaks / gaps designated as "common fragile sites" in cell population of clinically diagnosed patients of colorectal cancer patients in Nepalese population. These chromosomal changes including structural and numerical were compare to clinically healthy normal individual of same sex / age groups, act as controls for statistical analysis. The frequency of chromosomal aberration in cancer patients were significantly higher (p<0.001) when compare to normal individuals. The increased genetics instability probably either due to nutritional factor i.e. lack of folic acid component in diet--an essential component required for DNA synthesis or unknown environmental factor for such genetic disorder. The present study indicates aphidicolin high frequency of induced chromosome aberrations and "common fragile sites" because of late replication of DNA in mitosis in colorectal cancer patients suggesting these sites could be used as suitable marker for determining genetic predisposition in cancer patients.
染色体脆弱位点分布于整个人类基因组。在从结直肠癌患者外周血淋巴细胞获得的早中期/中期染色体中，评估了阿非科林介导的常见脆弱位点的表达频率及其他染色体变化。本研究首次揭示，在尼泊尔人群中临床诊断的结直肠癌患者细胞群体中，阿非科林诱导的染色体断裂/间隙（称为“常见脆弱位点”）的发生率很高，即6%。将这些包括结构和数量方面的染色体变化与相同性别/年龄组的临床健康正常个体进行比较，作为统计分析的对照。与正常个体相比，癌症患者的染色体畸变频率显著更高（p<0.001）。遗传不稳定性增加可能是由于营养因素，即饮食中缺乏叶酸成分（DNA合成所需的必需成分），或者是由于这种遗传疾病的未知环境因素。本研究表明，由于结直肠癌患者有丝分裂中DNA复制延迟，阿非科林诱导的染色体畸变和“常见脆弱位点”频率较高，这表明这些位点可作为确定癌症患者遗传易感性的合适标志物。
