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

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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 ΜM dithranol. Data were compared with those from experiments including additional pretreatments with 0.3 ΜM 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 ΜM dithranol, but was only 18.4% and 9.1% after pretreatment twice with 0.3 ΜM dithranol. This tolerance reaction in vitro, after repeated dithranol exposure of human keratinocytes, may be explained by a selective loss of drug-sensitive cells.

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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

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Farkas, B., Bonnekoh, B. & Mahrle, G. Repeated treatment with dithranol induces a tolerance reaction in keratinocytes in vitro. Arch Dermatol Res 283, 337–341 (1991). https://doi.org/10.1007/BF00376624

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