Reelfs, Olivier; Xu, Yao-Zhong; Massey, Andrew; Karran, Peter and Storey, Alan
Thiothymidine plus low-dose UVA kills hyperproliferative
human skin cells independently of their human papilloma virus status.
Molecular Cancer Therapeutics, 6
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The thymidine analogue 4-thiothymidine (S4TdR) is a photosensitizer for UVA radiation. The UV absorbance spectrum of S4TdR and its incorporation into DNA suggests that it might act synergistically with nonlethal doses of UVA to selectively kill hyperproliferative or cancerous skin cells. We show here that nontoxic concentrations of S4TdR combine with nonlethal doses of UVA to kill proliferating cultured skin cells. Established cell lines with a high fraction of proliferating cells were more sensitive than primary keratinocytes or fibroblasts to apoptosis induction by S4TdR/UVA. Although S4TdR plus UVA treatment induces stabilization of p53, cell death, as measured by apoptosis or clonal survival, occurs to a similar extent in both p53 wild-type and p53-null backgrounds. Furthermore, different types of human papilloma virus E6 proteins, which protect against UVB-induced apoptosis, have little effect on killing by S4TdR/UVA. S4TdR/UVA offers a possible therapeutic intervention strategy that seems to be applicable to human papilloma virus–associated skin lesions.
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