Elevated thymidine phosphorylase activity in psoriatic lesions accounts for the apparent presence of an epidermal "growth inhibitor," but is not in itself growth inhibitory.
An apparent tissue-specific growth inhibitor, or chalone, obtained from psoriatic lesions was tentatively identified in the 100-kDa fraction based upon inhibition of DNA synthesis, as measured by [3H]-thymidine uptake by a squamous cell carcinoma cell line, SCC 38. This fraction, however, failed to inhibit SCC 38 cell growth when assessed directly in a neutral red uptake assay. Characterization of the inhibitor of [3H]-thymidine uptake revealed it to have biochemical properties identical to thymidine phosphorylase: 1) molecular weight close to 100 kDa, 2) isoelectric point of 4.2, and 3) thymidine phosphorylase enzyme activity. Thus, we conclude that its ability to inhibit [3H]-thymidine uptake was due to thymidine catabolism rather than inhibition of DNA synthesis or growth inhibition. Examination of thymidine phosphorylase activity in keratome biopsies from psoriatic and normal skin demonstrated a twentyfold increase in activity in psoriatic lesions relative to non-lesional or normal skin. This increase in metabolism of thymidine was due to thymidine phosphorylase rather than uridine phosphorylase activity. The correlation between increased thymidine phosphorylase activity and increased keratinocyte proliferation in vitro (cultured) and in vivo (psoriasis), suggests that this enzyme may play a critical role in providing the thymidine necessary for keratinocyte proliferation.
Hammerberg
C
C
Department of Dermatology, University of Michigan Medical School, Ann Arbor.
Fisher
G J
GJ
Voorhees
J J
JJ
Cooper
K D
KD
D001706:Biopsy; D002294:Carcinoma, Squamous Cell / Q000378:metabolism; D002478:Cells, Cultured; D003600:Cytosol / Q000378:metabolism; D004817:Epidermis / Q000201:enzymology; D005347:Fibroblasts / Q000378:metabolism; D006131:Growth Inhibitors / Q000378:metabolism*; D006801:Humans; D008970:Molecular Weight; D011565:Psoriasis / Q000201:enzymology* / Q000473:pathology; D013936:Thymidine / Q000493:pharmacokinetics; D013939:Thymidine Phosphorylase / Q000378:metabolism*; D014316:Tritium; D014407:Tumor Cells, Cultured
D006131:Growth Inhibitors; D014316:Tritium; D013939:Thymidine Phosphorylase; D013936:Thymidine