EVIDENCE FOR UV-ASSOCIATED ACTIVATION OF TELOMERASE IN HUMAN SKIN

Telomerase activation plays a crucial role in the immortalization of h uman cells and carcinogenesis; however, the temporal and pathophysiolo gical aspects of the activation in vivo are poorly understood, We foun d telomerase activity not only in malignant tumors (91%) but also in m ost benign (60%) and premalignant (89%) skin tumors, This suggests the involvement of telomerase activation in a crucial biological step of human skin carcinogenesis, Because UV light is a major factor in skin carcinogenesis, we further examined telomerase activity in normal skin samples and in normal skin samples adjacent to benign, premalignant, and malignant skin lesions, Data for chronically sun-exposed body site s were compared with those for covered sites, Among normal skin sample s, 39% (26 of 67) had telomerase activity, and this activity was unrel ated to neighboring lesions but strongly associated with the level of sun exposure, Fifty-four % (21 of 39) of normal skin samples from chro nically sun-exposed sites were telomerase-positive, compared with only 12% (3 of 26) of samples from covered sites, When we examined telomer ase activity and CC to TT mutations at codons 247/8 of the p53 gene (w hich are considered to be UV specific) in the same normal skin samples , only 43% (7 of 16) of telomerase-positive normal skin samples at sun -exposed sites contained the p53 mutations, whereas all (7 of 7) of th e samples with UV-specific p53 mutations showed telomerase activity (P = 0.019). These data suggest that telomerase activation is involved a t an early stage of human skin carcinogenesis and that activation may precede the acquisition of UV-associated p53 mutations in the skin. Te lomerase activity was also found in plucked hair follicles and enzymat ically separated epidermis, which may be associated with the presence of stem cells in the skin.