Repeated treatment with dithranol induces a tolerance reaction in keratinocytes in vitro

Summary The hyperproliferative human keratinocyte line (HaCaT) was tested for dithranol tolerance (tachyphylaxis) at the cellular level. At day 4 after seeding, keratinocytes were treated with 0.3 or 1.0 M dithranol. Data were compared with those from experiments including additional pretreatments with 0.3 M at day 3, or at days 1 and 3. Protein content, DNA synthesis and protein synthesis (incorporation of ³H-thymidine and ¹⁴C-amino acids per protein) were determined at 24, 48 and 72 h after the last drug exposure. Protein content of attached cells decreased in relation to dose and frequency of treatments. Inhibition of DNA and protein synthesis (38.2% and 32.3%, respectively) also occurred 24 h after a single treatment with 0.3 M dithranol, but was only 18.4% and 9.1% after pretreatment twice with 0.3 M dithranol. This tolerance reaction in vitro, after repeated dithranol exposure of human keratinocytes, may be explained by a selective loss of drug-sensitive cells.This study was supported in part by the W.-Doerenkamp-Foundation. B. F. from the Department of Dermatology, Albert Szent-Györgyi Medical University of Szeged, Hungary, is a fellow of the Alexander-von-Humboldt-Foundation. On the occasion of the 65th birthday of Prof. Dr. Dr. h. c. G. K. Steigleder