The spectrum of mitochondrial DNA deletions is a ubiquitous marker of ultraviolet radiation exposure in human skin

Citation
Aj. Ray et al., The spectrum of mitochondrial DNA deletions is a ubiquitous marker of ultraviolet radiation exposure in human skin, J INVES DER, 115(4), 2000, pp. 674-679
Citations number
49
Categorie Soggetti
Dermatology,"da verificare
Journal title
JOURNAL OF INVESTIGATIVE DERMATOLOGY
ISSN journal
0022202X → ACNP
Volume
115
Issue
4
Year of publication
2000
Pages
674 - 679
Database
ISI
SICI code
0022-202X(200010)115:4<674:TSOMDD>2.0.ZU;2-I
Abstract
We and colleagues have suggested that deletions of mitochondrial DNA may be useful as a biomarker of ultraviolet radiation exposure in skin. In this s tudy using a southwestern approach involving monoclonal antibodies against thymine dimers we provide direct evidence for the presence of ultraviolet-i nduced damage in mitochondrial DNA purified from any nuclear DNA contaminat ion. Previous studies have been limited, as they have focused on the freque ncy of a single mitochondrial DNA deletion. Therefore we have addressed the question of the spectrum of mitochondrial DNA deletions in skin and whethe r this can be used as an index of overall DNA damage, We have used a long p olymerase chain reaction technique to determine the mitochondrial DNA delet ion spectrum of almost the entire mitochondrial genome in 71 split skin sam ples in relation to sun exposure. There was a significant increase in the n umber of deletions with increasing ultraviolet exposure in the epidermis (K ruskal-Wallis test, p = 0.0015) but not the dermis (p = 0.6376). The findin gs in the epidermis are not confounded by any age-dependent increases in mi tochondrial DNA deletions also detected by the long polymerase chain reacti on technique. The large spectrum of deletions identified in our study highl ights the ubiquitous nature and the high mutational load of mitochondrial D NA associated with ultraviolet exposure and chronologic aging. Compared wit h the detection of single deletions using competitive polymerase chain reac tion, we show that: long polymerase chain reaction is a sensitive technique and may therefore provide a more comprehensive, although not quantitative, index of overall mitochondrial DNA damage in skin.