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
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.