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Polypharmacy and sun exposure: Implications for mitochondrial DNA deletions in skin
Julia Montelin Powers1, Gillian Murphy2, Nikki Ralph2
1Mitochondrial Biology & Radiation Research Centre, Dept Life Sciences, IT Sligo, Sligo, Ireland.
Abstract:
Most somatic cells contain many copies of mitochondrial DNA (mtDNA). Because of both the high copy number and the lack of repair mechanisms available to mtDNA, damage to it largely goes unrepaired, and can accumulate over time. Large scale deletions are a recognised type of damage sustained by mtDNA as a consequence of exposure to the ultraviolet light in sunlight. A group of patients were identified as having abnormally high levels of either a 4977 base pair deletion (mtDNA4977) or 3895 base pair deletion (mtDNA3895), in mtDNA from sun exposed skin or skin suspected to be a non-melanoma skin cancer, but not in their non-sun exposed skin biopsies. In three of the four cases, skin cancer was ruled out due to histological testing. Additional factors from these patients' medical histories were studied, and it was noted that they shared diagnoses for multiple pathologies common to an older population, and that they were being treated with the same or related pharmaceuticals, including some that had been known to cause dermal side effects. Investigation into the biochemistry underlying the symptoms, the effects of sun exposure and side effects of the prescribed pharmaceuticals revealed a possible synergistic relationship leading to the localised high levels of mtDNA deletions.
Insights
Sun exposure and certain medications may synergistically increase mitochondrial DNA (mtDNA) deletions in sun-exposed skin. This damage, particularly large-scale deletions like mtDNA4977, occurs in skin cells and is linked to aging pathologies.
Area of Science:
- Mitochondrial DNA research
- Dermatology
- Genetics
Background:
- Mitochondrial DNA (mtDNA) is present in high copy numbers in somatic cells.
- mtDNA lacks efficient repair mechanisms, leading to unrepaired damage accumulation.
- Large-scale mtDNA deletions are a known consequence of ultraviolet (UV) light exposure.
Purpose of the Study:
- To investigate high levels of specific large-scale mtDNA deletions (mtDNA4977 and mtDNA3895) in sun-exposed skin.
- To explore potential contributing factors, including sun exposure, patient medical history, and pharmaceuticals.
Main Methods:
- Analysis of mtDNA deletions in skin biopsies from sun-exposed and non-sun-exposed sites.
- Histological examination to rule out non-melanoma skin cancer.
- Review of patient medical histories, including diagnoses and pharmaceutical treatments.
Main Results:
- Patients exhibited elevated levels of mtDNA4977 or mtDNA3895 deletions in sun-exposed skin, but not in non-exposed skin.
- Three of four cases were histologically confirmed as not having skin cancer.
- Patients shared common age-related pathologies and were treated with similar pharmaceuticals known to cause dermal side effects.
Conclusions:
- A potential synergistic relationship between sun exposure, pharmaceutical side effects, and localized mtDNA deletions is proposed.
- This interaction may contribute to the observed high levels of mtDNA damage in specific skin areas.
- Further investigation into the biochemical mechanisms is warranted.
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