1. ¹AntiCancer Inc., San Diego, California, USA
2. ²Department of Dermatology, Kitasato University School of Medicine, Sagamihara, Japan
3. ³Department of Surgery, University of California San Diego, San Diego, California, USA

Correspondence: Dr Robert M. Hoffman, AntiCancer Inc., 7917 Ostrow Street, San Diego, California 92111, USA. E-mail: all@anticancer.com

Received 1 March 2006; Revised 10 May 2006; Accepted 6 June 2006; Published online 13 July 2006.

Abstract

Chemotherapy-induced alopecia is a major problem in clinical oncology. Doxorubicin, a widely used cancer chemotherapy drug, induces disruption of the hair cycle and subsequent alopecia. We show in this report that doxorubicin causes disruption of the hair-follicle-associated blood vessel network resulting in a greatly reduced density of these blood vessels. Dystrophic hair follicles were also observed with abnormal melanogenesis in the mice treated with doxorubicin. Visualization of the effect of doxorubicin on hair-follicle angiogenesis was made possible by the use of transgenic mice in which green fluorescent protein was driven by regulatory elements of the nestin gene (ND-GFP). In these transgenic mice, the hair-follicle stem cells and the follicle structure as well as the blood vessels associated with the hair follicles express ND-GFP. The hair-follicle stem cells did not appear to be affected by doxorubicin, which may explain why hair regrows after chemotherapy. These results suggest that inhibition of hair-follicle-associated angiogenesis by doxorubicin may be an important factor in hair-follicle dystrophy associated with chemotherapy-induced alopecia. The ND-GFP mouse model is thus useful for the study of the role of angiogenesis in the hair-follicle cycle and the effect of drugs on processes associated with chemotherapy-induced alopecia.