烟草悬凝物诱导人支气管上皮细胞系恶性转化过程中染色体畸变

Chromosome aberration during malignant transformation of human bronchial epithelial cells induced by cigarette smoke condensate

目的:研究染色体畸变与细胞恶性转化之间的关系,探讨烟草致肺癌的发生机制.方法:将细胞分为2组:对照组为正常人支气管上皮细胞;实验组为经烟草悬凝物(CSC)处理P15(Passage,P),P20,P25,P30,P35及P38细胞.采用细胞遗传学方法观察染毒后CSC诱导的人支气管上皮细胞染色体畸变情况.结果:对照组各代细胞二倍体占细胞总数94%～98%,异倍体及多倍体细胞总数为17个,发生率为3%,而且能够在传代过程中基本保持核型及染色体数目稳定.实验组细胞从P15开始逐渐失去正常2n=46核型,二倍体细胞从83%递减至53%,异倍体及多倍体细胞总数196个,发生率为32.7%,与对照组相比较,差异具有统计学意义(χ2=152.5552,P<0.01).对照组各代细胞结构畸变的发生细胞总数6个,发生率为1%;而实验组各代细胞结构畸变的发生细胞总数60个,发生率为10%,与对照组比较差异具有统计学意义(χ2=40.0834,P<0.01);并在P38出现了内复制现象和环状染色体,发生率分别为4%和1%.结论:CSC可影响BEP-2D细胞染色体稳定性,使其发生畸变并最终促使细胞向恶性化方向转化;并在P15就发生染色体畸变.推测染色体畸变可能是早期事件.

AIM： To study the relationship between chromosome aberration and malignant transformation of immortalized human bronchial epithelial （BEP-2D）cells and to explore the mechanisms of smoking-induced lung cancer. METHODS： Cells were divided into control group and experimental group, with immortalized human bronchial epithelial （BEP-2D）cells and BEP-2D cells （including P15, P20, P25, P30, P35 and P38 cells ）treated by cigarette smoke condensate （ CSC ） , respectively. Cytogenetics methods were used to analyze the chromosome aberration of BEP- 2D cells treated by CSC. RESULTS： The cells in control group kept a relatively stable pattern of karyotypes and chromosome numbers, with a ratio of 94% - 98% for the cells of diploid and with 17 （3% , in percentage）cells of aneuploid and polyploidy. The cells in experimental group gradually lost their normal diploid karyotypes （beginning from P15 cells）. The ratio of diploid cells decreased from 83% to 53% and the number of aneuploid and polyploidy cells was 196 （32.7% , in percentage）, with statistically significant difference （ X^2 = 152. 5552, P 〈 0. 01 ）. The number of cells with chromosome aberration was 6 （ 1% in percentage） and 60 （10% in percentage）respectively in control group and in experimental group, with statistically significant difference （ X^2 = 40. 0834, P 〈 0.01 ）. Additionally, the phenomena of endoradiosonde and circular chromosome was found in P38 cells in experimental group, with a ratio of 4% and 1%, respectively.CONCLUSION： Cigarette smoke condensate may result in the instability of chromosomes of BEP-2D cells, with an inducement of aberration and malignant transformation. The chromosome aberration, found in the P15 cells, could be taken as an early event in the process of malignant transformation of BEP-2D cells.