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Investigating the role of melanin in UVA/B- and hydrogen peroxide-induced cellular and mitochondrial ROS production and mitochondrial DNA damage in human melanoma cells

Lookup NU author(s): Dr Helen Swalwell, Dr Jennifer Latimer, Professor Mark Birch-MachinORCiD

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Abstract

Skin cancer incidence is dramatically increasing world-wide with exposure to ultraviolet radiation (UVR) a predominant factor. The UVA component initiates oxidative stress in human skin although its exact role in the initiation of skin cancer, particularly malignant melanoma remains unclear and is controversial since there is evidence for a melanin-dependent mechanism in UVA-linked melanoma studies. Non-pigmented (CHL-1, A375), moderately pigmented (FM55, SKmel23) and highly pigmented (FM94, hyper-pigmented FM55) human melanoma cell lines have been used to investigate UVA-induced production of reactive oxygen species using FACS analysis, both at the cellular (dihydrorhodamine-123) and mitochondrial (MitoSOX) level where most cellular stress is generated. For the first time, assessment of downstream mtDNA damage (utilising a long-qPCR assay) has been investigated. Using UVA, UVB and H₂O₂ as cellular stressors, we have explored the dual role of melanin as a photoprotector and photosensitiser. The presence of melanin has no influence over cellular oxidative stress generation whereas in contrast, melanin protects against mitochondrial superoxide generation and mtDNA damage (one-way ANOVA with post-hoc Tukey’s analysis P<0.001). We show that if melanin binds directly to DNA, it acts as a direct photosensitiser of mtDNA damage during UVA irradiation (P <0.001), providing evidence for the dual role of melanin.

Publication metadata

Author(s): Swalwell H, Latimer J, Haywood RM, Birch-Machin MA

Publication type: Article

Publication status: Published

Journal: Free Radical Biology and Medicine

Year: 2012

Volume: 52

Issue: 3

Pages: 626-634

Print publication date: 08/12/2011

ISSN (print): 0891-5849

ISSN (electronic): 1873-4596

Publisher: Elsevier Inc.

URL: http://dx.doi.org/10.1016/j.freeradbiomed.2011.11.019

DOI: 10.1016/j.freeradbiomed.2011.11.019

Notes: Key material contribution as the PI of the cancer research UK grant that funded this work+ wrote the paper (corresponding author) + designed the experiments to be carried out in my group. Journal is top in its field (excepting review based journals)

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