Smoking-associated mitochondrial DNA mutations in human hair follicles.
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.
Liu
C S
CS
Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, Republic of China.
Kao
S H
SH
Wei
Y H
YH
D000328:Adult; D000368:Aged; D001482:Base Composition; D004249:DNA Damage; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000235:genetics* / Q000302:isolation & purification; D018859:Hair Follicle / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008175:Lung Neoplasms / Q000737:chemistry / Q000235:genetics; D008297:Male; D008875:Middle Aged; D012091:Repetitive Sequences, Nucleic Acid; D012907:Smoking / Q000009:adverse effects* / Q000235:genetics*
D004272:DNA, Mitochondrial