甲醛对人支气管上皮细胞系转化和染色体不稳定性影响的研究

Transformation and chromosomal instability of human tracheal epithelial cells induced by formaldehyde

目的为探讨化学致癌的机制,揭示恶性转化与染色体不稳定性之间的关系,本研究考察甲醛对人支气管上皮细胞系转化和染色体稳定性的影响。方法用甲醛作为诱导剂,以液体染毒后测定BEAS-2B细胞的LC50,以低剂量(20%LC50)对细胞进行诱导,观察细胞生长特性改变并筛选诱导克隆。然后用细胞遗传学方法(G带染色法)考察诱导细胞染色体畸变的情况。结果甲醛作用后细胞生长速度加快,且呈现无限增殖趋势。在后期(15代)具有很强的锚着独立性生长能力,表明诱导细胞已发生慢性转化。诱导细胞核型由2倍体转化为近2倍体、非整倍体和多倍体等核型同时存在,染色体稳定性降低,呈现丢失、内复制、易位、断裂、双/三着丝粒,并伴有大量非稳定性畸变。结论甲醛可使BE-AS-2B细胞发生转化,并影响细胞染色体的稳定性,使其发生畸变并向恶性化方向发展。

Objective To explore the mechanisms of chemical carcinogenesis and the relationship between malignant transformation and genomic/chromosomal instability of human bronchial epithelial cell line by formaldehyde. Methods BEAS-2B cell line was toxicated by formaldehyde and the LC50 of formaldehyde was tested by MTT assay. BEAS-2B cells were induced by formaldehyde at 20% LC50, and the transformation of BEAS-2B cells was identified and induced clones were selected. By G-banding technique, the metaphase modal chromosome number, karyotypes and nonrandom structural change of induced cell strains were analyzed. Results The growth rate of BEAS-2B cells induced by formaldehyde was significantly increased. The induced cells showed a trend of infinite proliferation and the anchorage independent growth was seen in 15^th generation cells. As compared with the relatively stable pseudodiploid karyotype of BEAS-2B cells, most of induced cells were triploid and/or tetraploid karyotypes and their chromosome 14 had lost two copies of chromosome replaced by the other two. They also had high frequency of unstable aberration （39%）, including chromosome loss, endoduplication, translocation, breakage, two and/or three centromeres etc.. Conclusion The formaldehyde could lead to progression of malignant transformation and result in genomic instability of human bronchial epithelial cells in vitro.