Effect of smoking on DNA damage and chromosome aberration in alveolar macrophage

我们研究了吸烟对肺泡巨噬细胞基因（DNA）损伤和染色体畸变的影响，研究了吸烟增强肺泡巨噬细胞02的生成。吸烟可引起肺泡巨噬细胞DNA损伤和染色体畸变。肺泡巨噬细胞的所有染色体均出现染色体畸变。我们从染色体异常点检测了约43000个基因，与不吸烟相比，检测到畸变点的基因总数为280个，表达量增加2倍以上的基因数量为127个，而表达量减少2倍以上的基因数量为153个。吸烟增加的基因为趋化因子基因，吸烟减少的基因为黏附分子和前列环素合成酶。此外，吸烟在肺组织DNA中检测到与癌变密切相关的8-OHdG的增加，在细支气管粘膜上皮细胞中检测到8-OHdG的表达。上述结果提示，吸烟对肺泡巨噬细胞免疫功能的抑制机制可能与O_2^-通过H_2O_2产生的OH引起DNA损伤有关，其结果可能是抑制抗原提呈分子的表达和抑制细胞因子的产生。提示吸烟引起肺泡巨噬细胞过度活性氧（ROS）生成8-OHdG的增加和免疫功能的抑制与肺癌的发生有关。此外，香烟烟雾对肺泡巨噬细胞免疫功能的抑制影响了B细胞的早期阶段，其结果抑制了抗体的产生，这些结果可能对感染有增加的可能性。

We examined concerning the effect of the smoking on the gene (DNA) damage and the chromosome aberration of the alveolar macrophage from 02- production of the alveolar macrophage being strengthened by smoking. The DNA damage and chromosome aberration of the alveolar macrophage was caused by smoking. The chromosome aberration of was presented in all the chromosomes in alveolar macrophage. We examined about 43000 genes from unusual points of chromosomes, the number of total genes which aberration points were detected was 280 genes compared with non-smoking, and the number of genes which increased more than 2 times expression was 127, however, genes expressions which decreased more than 2 times were 153 compared with non-smoking. Specially, the gene expression increased by smoking was chemokine genes, conversely the gene expressions decreased by smoking were adhesion molecules and the prostacyclin synsetiyze enzyme. Moreover, increase in 8-OHdG which is closely associated with carcinogenesis was detected in DNA of lung tissue by smoking, the expression of 8-OHdG was recognized on mucous epithelial cells in bronchiole. These results suggested that the mechanism of inhibition of immune functions in alveolar macrophage by smoking was associated with caused DNA damage by generated OH through H_2O_2 from O_2^-, and its results was occurred inhibition of expression of antigen presenting molecule and inhibition of cytokine production. It was suggested that increase in the generation of 8-OHdG by excessively reactive oxygen species (ROS) from alveolar macrophage by smoking and inhibition of immune function were related to incidence of lung cancer. Furthermore, the repression of immune function of alveolar macrophage by cigarette smoke influenced the early stage of B cell, and its result inhibited antibody production, and these results may be present the possibility to increase for infection.