Liu C S, Kao S H, Wei Y H
Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, Republic of China.
Environ Mol Mutagen. 1997;30(1):47-55. doi: 10.1002/(sici)1098-2280(1997)30:1<47::aid-em7>3.0.co;2-9.
The mitochondrial DNA (mtDNA) of hair follicles was used for studying the genotoxicity of smoking-mediated carcinogens. We determined the incidences of the 4,977 bp and 7,436 bp mtDNA deletions, tandem duplication in the D-loop region and the proportion of the 4,977 bp deleted mtDNA (dmtDNA) in the total DNA of hair follicles from 213 male non-smokers and 74 male smokers, respectively. Twenty-three patients with lung cancer were also investigated. We found that the current cigarette smokers had a 3.1 times higher average incidence of the 4,977 bp dmtDNA (RR: 3.1, P < 0.001) as compared with non-smokers, and this mtDNA deletion was especially prevalent in the old heavy smokers. For the smokers of the age above 70, the average incidence of the 4,977 bp dmtDNA was 3.7 times higher in the group with a smoking index of 401-800 (RR: 3.7, P < 0.005) and 3.2 times higher in the group with a smoking index greater than 800 (RR: 3.2, P < 0.005). However, there was no statistically significant relationship between the incidence of the 7,436 bp dmtDNA and the smoking index, although there was a mild increase in the percentage of the 7,436 bp dmtDNA with the increase of the consumption of cigarettes. No tandem duplication of mtDNA in the D-loop region was disclosed in either smokers or non-smokers group. The proportions of the 4,977 bp dmtDNA in hair follicles were found to correlate with age, but did not keep increasing with cigarette consumption except in the group of subjects with a smoking index of less than 400. On the other hand, we found that the average proportion of the 4,977 bp dmtDNA in the hair follicles was 1.201 +/- 0.371% for the patients with lung cancer who had a smoking index greater than 400, while that was only 0.146% for the age-matched healthy smokers with the same smoking index. In conclusion, the high incidence of the 4,977 bp dmtDNA of hair follicles is not only associated with aging but also correlated with the amount of cigarette smoking. A high proportion of the 4,977 bp dmtDNA in the hair follicles may be considered one of the molecular events that are associated with the occurrence of smoking-associated cancers.
毛囊的线粒体DNA（mtDNA）被用于研究吸烟介导的致癌物的遗传毒性。我们分别测定了213名男性非吸烟者和74名男性吸烟者毛囊中4977bp和7436bp的mtDNA缺失、D环区域的串联重复以及4977bp缺失的mtDNA（dmtDNA）在毛囊总DNA中的比例。还对23名肺癌患者进行了调查。我们发现，与非吸烟者相比，当前吸烟者的4977bp dmtDNA平均发生率高3.1倍（相对风险：3.1，P<0.001），并且这种mtDNA缺失在老年重度吸烟者中尤为普遍。对于70岁以上的吸烟者，吸烟指数为401 - 800的组中4977bp dmtDNA的平均发生率高3.7倍（相对风险：3.7，P<0.005），吸烟指数大于800的组中高3.2倍（相对风险：3.2，P<0.005）。然而，尽管随着香烟消费量的增加，7436bp dmtDNA的百分比有轻微上升，但7436bp dmtDNA的发生率与吸烟指数之间没有统计学上的显著关系。在吸烟者或非吸烟者组中均未发现D环区域的mtDNA串联重复。发现毛囊中4977bp dmtDNA的比例与年龄相关，但除了吸烟指数小于400的受试者组外，并不随香烟消费量的增加而持续上升。另一方面，我们发现吸烟指数大于400的肺癌患者毛囊中4977bp dmtDNA的平均比例为1.201±0.371%，而吸烟指数相同的年龄匹配健康吸烟者仅为0.146%。总之，毛囊中4977bp dmtDNA的高发生率不仅与衰老有关，还与吸烟量相关。毛囊中高比例的4977bp dmtDNA可能被认为是与吸烟相关癌症发生相关的分子事件之一。
