Alopecia is a common side effect of cancer chemotherapy, and to date,
little progress has been made in alopecia prevention or treatment. The
present studies were undertaken to topographically localize the site
of injury in the hair follicle after doxorubicin (DXR) administration
and to investigate the mechanism of DXR-induced alopecia. Tissue sampl
es of head and proximal neck skin obtained from newborn rats treated w
ith DXR were histologically examined by light and electron microscopy
and stained by the terminal deoxynucleotidyl transferase-mediated deox
yuridine triphosphate nick-end labeling method. Light microscopy revea
led pyknotic cells in the matrix and in the upper bulb and a decrease
in the number of mitotic cells. Terminal deoxynucleotidyl transferase-
mediated deoxyuridine triphosphate-digoxigenin nick-end labeling analy
sis evidenced cells with nuclear staining indicative of apoptosis, as
confirmed by ultrastructural analysis. Kinetics studies indicated that
even a single DXR treatment induced apoptosis and a decrease in mitot
ically active cells. Our data show that DXR treatment induces injury i
n a cell subset localized in the hair matrix. The successful preventio
n of drug-induced alopecia in patients may depend on the selective pro
tection of these cells of the hair follicle.