Skip Navigation
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

National Institute of Environmental Health Sciences

Use this QR code to view the newest version of this document
Use this QR code to view the newest version of this document

Your Environment. Your Health.

Publication Detail

Title: Antioxidant/stress response in mouse epidermis following exposure to nitrogen mustard.

Authors: Wahler, Gabriella; Heck, Diane E; Heindel, Ned D; Laskin, Debra L; Laskin, Jeffrey D; Joseph, Laurie B

Published In Exp Mol Pathol, (2020 06)

Abstract: Nitrogen mustard (NM) is a highly reactive bifunctional alkylating agent that induces inflammation, edema and blistering in skin. An important mechanism mediating the action of NM and related mustards is oxidative stress. In these studies a modified murine patch-test model was used to analyze DNA damage and the antioxidant/stress response following NM exposure in isolated epidermis. NM (20 μmol) was applied to glass microfiber filters affixed to a shaved dorsal region of skin of CD-1 mice. NM caused structural damage to the stratum corneum as reflected by increases in transepidermal water loss and skin hydration. This was coordinate with edema, mast cell degranulation and epidermal hyperplasia. Within 3 h of NM exposure, a 4-fold increase in phosphorylated histone H2AX, a marker of DNA double-stranded breaks, and a 25-fold increase in phosphorylated p53, a DNA damage marker, were observed in the epidermis. This was associated with a 40% increase in 8-oxo-2'-deoxyguanosine modified DNA in the epidermis and a 4-fold increase in 4-hydroxynonenal modified epidermal proteins. At 12 h post NM, there was a 3-75 fold increase in epidermal expression of antioxidant/stress proteins including heme oxygenase-1, thioredoxin reductase, superoxide dismutase, glutathione reductase, heat shock protein 27 and cyclooxygenase 2. These data indicate that NM induces early oxidative epidermal injury in mouse skin leading to an antioxidant/stress response. Agents that enhance this response may be useful in mitigating mustard-induced skin injury.

PubMed ID: 32113906 Exiting the NIEHS site

MeSH Terms: Alkylating Agents/pharmacology; Alkylating Agents/toxicity; Animals; Antioxidants/metabolism*; Apoptosis/drug effects; Cyclooxygenase 2/genetics; DNA Damage/drug effects; Epidermis/drug effects; Epidermis/metabolism*; Glutathione Reductase/genetics; HSP27 Heat-Shock Proteins/genetics; Heme Oxygenase-1/genetics; Humans; Inflammation/chemically induced; Inflammation/genetics; Inflammation/pathology; Mechlorethamine/pharmacology*; Mechlorethamine/toxicity; Mice; Oxidative Stress/drug effects; Phosphorylation/drug effects; Skin/drug effects; Skin/metabolism; Stress, Physiological/genetics*; Superoxide Dismutase/genetics; Thioredoxin-Disulfide Reductase/genetics

Back
to Top