CHRONICALLY ULTRAVIOLET-EXPOSED HUMAN SKIN SHOWS A HIGHER MUTATION FREQUENCY OF MITOCHONDRIAL-DNA AS COMPARED TO UNEXPOSED SKIN AND THE HEMATOPOIETIC SYSTEM

Normal ageing processes are associated with an accumulation of mutatio ns within the mitochondrial (mt) DNA, The most frequent mutation is a 4977 base pair (bp) deletion known as common deletion, In order to tes t the hypothesis that chronically sun-exposed skin is characterized by an increased mutation frequency of mtDNA, the mutation frequency of t he common deletion between skin and another replicating tissue (the he matopoietic system) and chronically sun-exposed versus sun-protected s kin was compared in the same individuals, This was done by comparing t he amount of mutated mtDNA molecules with the whole mitochondrial geno me in the same specimen with a semiquantitative polymerase chain reati on method, thus allowing direct comparison of different tissues. In al l skin specimens the common deletion could be observed, In contrast on ly 3 of 10 blood samples revealed detectable amounts of the common del etion, Comparison of sun-exposed versus sun-protected skin exhibited a higher content of the common deletion in sun-exposed skin in 7 of 10 individuals, Additionally, a hitherto undescribed mtDNA mutation was d etected exclusively in human skin, These studies indicate that exposur e of human skin to solar radiation leads to an accumulation of mtDNA m utations, possibly via oxidative damage, which may play an important r ole in photoageing.