Daunomycin accumulation and induction of programmed cell death in rat hair follicles

• Published in: Cell and tissue research Vol. 337; no. 3; pp. 429 - 438
• Main Authors: Shin, Masashi, Larsson, Lars-Inge, Hougaard, David M, Fujiwara, Kunio
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Berlin/Heidelberg : Springer-Verlag 01.09.2009; Springer-Verlag; Springer Nature B.V
• Subjects: Animals; Antibiotics; Antibiotics, Antineoplastic - pharmacokinetics; Antibiotics, Antineoplastic - pharmacology; Apoptosis; Apoptosis - drug effects; Biomedical and Life Sciences; Biomedicine; Caspase 3 - metabolism; Cell death; Daunorubicin - pharmacokinetics; Daunorubicin - pharmacology; DNA Fragmentation - drug effects; Hair; Hair Follicle - drug effects; Hair Follicle - enzymology; Hair Follicle - metabolism; Hair Follicle - ultrastructure; Human Genetics; Immunohistochemistry; In Situ Nick-End Labeling; Male; Molecular Medicine; Proteomics; Rats; Rats, Wistar; Regular Article; Rodents; Time Factors; Immunocytochemistry; Distribution; Hair follicle; Daunomycin; Programmed cell death; Double-immunostaining; Monoclonal antibody; Rat (Wistar, male)
• ISSN: 0302-766X; 1432-0878
• DOI: 10.1007/s00441-009-0840-8

The anthracycline antibiotic daunomycin (DM) is useful for the treatment of leukemia but has side-effects such as alopecia. Using immunocytochemistry, we show that, after a single i.v. injection, DM accumulates in the nuclei of matrix cells and in the outer root sheath of hair follicles. DM-positive matrix cells are detectable up to 48 h after injection and exhibit a characteristic granular morphology, which is not observed in saline-injected controls. TUNEL-staining has revealed that DM injection induces programmed cell death (PCD) in rat hair follicles. Cells undergoing PCD are detectable as late as 5 days postinjection in both the matrix and outer root sheath. Newly developed double-staining has shown that some of the DM-positive matrix cell nuclei are also TUNEL-positive. Staining for activated caspase-3 has demonstrated immunopositive cells following DM administration both in the matrix and in the outer root sheath. Ultrastructural immunocytochemistry has shown the presence of DM-positive cells with two different types of morphology. About half of the immunopositive cells exhibit a morphology typical of classical apoptosis (PCD type 1), whereas the other half show signs of autophagic cell death (PCD type 2). Interestingly, little, if any, DM accumulation or apoptosis has been detected in the dermal hair papillae. This may have a bearing on potential regeneration of the hair follicles. Thus, DM accumulates in a characteristic pattern in hair follicles. This accumulation is associated with the induction of two morphologically distinct forms of PCD.