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p53 Is Essential for Chemotherapy-induced Hair Loss¹

Department of Dermatology, Boston University School of Medicine, Boston, Massachusetts 02118 [V. A. B., F. S., N. V. B., B. A. G.]; Department of Molecular Genetics, University of Illinois at Chicago, Chicago, Illinois 60607 [E. A. K., P. G. K., A. V. G.]; Department of Dermatology, Johannes Gutenberg University, D-55101 Mainz, Germany [F. S., M. M.]; and Quark Biotech, Inc., Pleasanton, California 94566 [P. G. K.]

Anticancer drugs stimulate apoptosis in the hair follicles (HF) and cause hair loss, the most common side effect of chemotherapy. In a mouse model for chemotherapy-induced hair loss, we demonstrate that p53 is essential for this process: in contrast to wild-type mice, p53-deficient mice show neither hair loss nor apoptosis in the HF keratinocytes that maintained active proliferation after cyclophosphamide treatment. HF in p53 mutants are characterized by down-regulation of Fas and insulin-like growth factor-binding protein 3 and by increased expression of Bcl-2. These observations indicate that local pharmacological inhibition of p53 may be useful to prevent chemotherapy-associated hair loss.

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