Human skin mitochondrial DNA deletions associated with light exposure.
By polymerase chain reaction technique and DNA sequencing, we demonstrated the existence of multiple deletions in the mitochondrial DNA (mtDNA) of human skin tissues obtained from different body sites of an 86-year-old male farmer. We examined four types of skin tissues of different physiologic conditions, including sun-exposed, nonexposed, precancerous, and cancerous. The results showed that the common age-related 4977-base-pair (bp)-deleted mtDNA was present in different proportions in all the tissues examined. Quantitative PCR revealed that the amount of the 4977-bp-deleted mtDNA was associated with the physiologic conditions of the skin tissues. The sun-exposed skin tissues harbored higher level of the 4977-bp-deleted mtDNA (12.5%) than the nonexposed normal aged skin tissues (0.4%). On the other hand, in all the exposed skin tissues examined, the slower growing aged skin tissues harbored higher level of the 4977-bp-deleted mtDNA than the faster growing skin tissues in cancerous and precancerous skin tissues. In addition, we found at least four new deletions in the aforementioned different body sites with sizes of 7031, 7150, 7288, and 7485 bp, respectively. These findings provide an evidence of photooxidation-induced mtDNA mutations, since the deletions deposit in different patterns and proportions in different skin tissues of the patient. These findings suggest that, besides the intrinsic formation and accumulation of mtDNA deletions in human tissues during normal aging process, physiological and environmental factors may also play important roles in eliciting the deposit of deleted mtDNA molecules in the tissue cells.
Pang
C Y
CY
Department and Institute of Biochemistry, National Yang-Ming Medical College, Taipei, Taiwan, R.O.C.
Lee
H C
HC
Yang
J H
JH
Wei
Y H
YH
D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D000382:Agricultural Workers' Diseases / Q000235:genetics; D001483:Base Sequence; D004249:DNA Damage; D004272:DNA, Mitochondrial / Q000235:genetics* / Q000528:radiation effects*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D011230:Precancerous Conditions / Q000235:genetics; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion; D012867:Skin / Q000528:radiation effects*; D012878:Skin Neoplasms / Q000235:genetics; D013472:Sunlight / Q000009:adverse effects*
D004272:DNA, Mitochondrial