Aspirin Protects Melanocytes and Keratinocytes against UVB-Induced DNA Damage In Vivo.

Abstract

UVR promotes skin cancer through multiple mechanisms, including induction of inflammation, oxidative stress, and DNA damage such as 8-oxoguanine and cyclobutane pyrimidine dimers. We investigated whether the anti-inflammatory activities of aspirin (acetylsalicylic acid [ASA]) could protect against UVB-induced DNA damage and skin carcinogenesis. ASA reduced UVB-induced 8-oxoguanine and cyclobutane pyrimidine dimers in Melan-A melanocytes and HaCaT keratinocytes. Skin from UVB-irradiated C57BL/6 mice receiving 0.4 mg ASA daily by gavage exhibited less inflammation, fewer sunburn cells, and reduced 8-oxoguanine lesions than skin from irradiated control animals. ASA similarly reduced UVB-induced sunburn cells, 8-oxoguanine, and cyclobutane pyrimidine dimer lesions in skin of melanoma-prone TN61R mice, and this was associated with decreased prostaglandin E2 in plasma and skin. These effects of ASA, however, did not delay melanoma onset in TN61R mice exposed to a single neonatal dose of UVB. In SKH1-E mice prone to squamous cell carcinoma, ASA reduced plasma and skin prostaglandin E2 levels and indices of UVB-induced DNA damage and delayed squamous cell carcinoma onset induced by chronic UVB. These results indicate that ASA can protect against UVB-induced inflammation in skin and reduce UVB-induced DNA damage in both melanocytes and keratinocytes. These effects translated into greater chemopreventive efficacy for UVB-induced squamous cell carcinoma than melanoma mouse models.

• Authors: Hafeez Rahman, Dileep Kumar, Tong Liu, Nwanneka Okwundu, David Lum, Scott R Florell, Christin E Burd, Kenneth M Boucher, Matthew W VanBrocklin, Douglas Grossman
• Journal: The Journal of investigative dermatology (J Invest Dermatol) Vol. 141 Issue 1 Pg. 132-141.e3 (01 2021) ISSN: 1523-1747 [Electronic] United States
• PMID: 32569596 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Aspirin

Topics

• Animals
• Anti-Inflammatory Agents, Non-Steroidal (pharmacology)
• Aspirin (pharmacology)
• DNA Damage
• Disease Models, Animal
• Keratinocytes (drug effects, pathology)
• Melanocytes (drug effects, pathology)
• Melanoma (drug therapy, metabolism, pathology)
• Mice
• Mice, Inbred C57BL
• Neoplasms, Experimental
• Oxidative Stress
• Skin (metabolism, pathology)
• Skin Neoplasms (drug therapy, genetics, pathology)
• Ultraviolet Rays (adverse effects)