Repeated treatment with dithranol induces a tolerance reaction in keratinocytes in vitro.
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 microM dithranol. Data were compared with those from experiments including additional pretreatments with 0.3 microM 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 microM dithranol, but was only 18.4% and 9.1% after pretreatment twice with 0.3 microM dithranol. This tolerance reaction in vitro, after repeated dithranol exposure of human keratinocytes, may be explained by a selective loss of drug-sensitive cells.
Department of Dermatology, University of Cologne, Federal Republic of Germany.
B
B
Farkas
B
B
Bonnekoh
G
G
Mahrle
D000875:Anthralin / Q000494:pharmacology*; D002460:Cell Line; D004247:DNA / Q000096:biosynthesis; D004361:Drug Tolerance; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects*; D014176:Protein Biosynthesis
D004247:DNA; D000875:Anthralin