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Nitrogen Mustard Induces DNA Damage and Structural Changes in Mouse Skin Hair Follicles
Author(s) -
Composto Gabriella,
Kim Sally,
Heck Diane,
Laskin Jeffrey,
Laskin Debra,
Joseph Laurie
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.766.7
Subject(s) - proliferating cell nuclear antigen , epidermis (zoology) , hair follicle , infundibulum , dermis , biology , eschar , outer root sheath , chemistry , microbiology and biotechnology , endocrinology , pathology , immunology , anatomy , immunohistochemistry , medicine
Nitrogen mustard (NM) is a potent skin vesicant. Evidence suggests that the pilosebaceous unit in the skin is a target for NM. To assess this, we analyzed changes in hair follicles and sebaceous glands in mouse skin following NM exposure. Dorsal skin of female CD‐1 mice was exposed to 77 ng NM for 6 min, and harvested 1‐5 d later. Control (CTL) skin contained sebaceous glands expressing fatty acid synthase (FAS), a marker for sebum production. Proliferating cell nuclear antigen (PCNA, marker of cellular division) and keratin‐10 (K‐10, marker of cellular differentiation) were expressed in the hair outer root sheath (ORS) and infundibulum of CTL skin. One d post NM, FAS, PCNA and K‐10 expression was decreased in sebaceous glands, ORS, and infundibulum, respectively, while phospho‐H2A.X, a marker for double strand DNA breaks, was evident in the ORS and basal epidermis. By 2 d, an eschar formed; there were reduced numbers of pilosebaceous units within the eschar and this was associated with increased expression of phospho‐H2A.X in hyperplastic interfollicular epidermis (IFE). Three days post‐NM, low levels of FAS, PCNA, and K‐10 were expressed in the pilosebaceous units at the wound edge. By 4 d, small pilosebaceous units within the neo‐epidermis expressed increased levels of FAS, PCNA and K‐10, while decreased levels of phospho‐H2A.X were observed within the IFE. By 5 d, wound healing was evident with increased FAS and K‐10 expression in the sebaceous glands and infundibulum, respectively. PCNA was also increased in the ORS, while phospho‐H2A.X was decreased. These data indicate that the pilosebaceous unit is an important target contributing to NM‐induced skin injury. Support: NIH AR055073.