Celina Pihl, F. Andersen, Peter Bjerring, M. Haedersdal, C. Lerche
{"title":"Efficacy of combinational treatment versus nicotinamide monotherapy in the prevention of ultraviolet radiation-induced skin cancer.","authors":"Celina Pihl, F. Andersen, Peter Bjerring, M. Haedersdal, C. Lerche","doi":"10.1159/000538445","DOIUrl":null,"url":null,"abstract":"INTRODUCTION\nUltraviolet radiation (UVR) is the primary risk factor for keratinocyte carcinomas (KC). Oral supplementation with nicotinamide (NAM; NAM-mono) is reported to reduce the formation of new KCs. NAM's photoprotection is mediated by enhanced DNA repair. We wanted to explore whether NAM in combination with anti-proliferative (Metformin; Met) or antioxidant (Phloroglucinol; PG) compounds could potentially enhance its photoprotective effects.\n\n\nMETHODS\nHairless mice (C3.Cg-Hrhr/TifBomTac) were treated orally with either a standard dose of NAM monotherapy (600 mg/kg), or NAM (400 mg/kg) combined with Met (200 mg/kg) (NAM-Met) or PG (75 mg/kg) (NAM-PG). Mice were irradiated with 3.5 standard erythema doses of UVR three times per week to induce tumour development. Photoprotective effects were based on i) tumour onset of the first three tumours, ii) skin photodamage, and iii) DNA damage (cyclobutane pyrimidine dimers [CPDs] and pyrimidine-pyrimidone (6-4) photoproducts [6-4PPs]).\n\n\nRESULTS\nAll mice treated with NAM demonstrated a delay in tumour onset and reduced tumour burden compared to the UV control group (NAM, NAM-Met, NAM-PG vs. UV control: p ≤ 0.015). NAM-mono and NAM-PG increased time until all three tumours with no difference between them, indicating a similar degree of photoprotection. NAM-mono had no effect on DNA damage compared to the UV control group (p > 0.05), whereas NAM-PG reduced 6-4PP lesions (p < 0.01), but not CPDs (p > 0.05) compared to NAM-mono. NAM-Met delayed the onset of the third tumour compared to the UV control but demonstrated a quicker onset compared to NAM-mono, suggesting inferior photoprotection compared to nicotinamide monotherapy.\n\n\nCONCLUSION\nNAM-PG was as effective in delaying UVR-induced tumour onset as NAM-mono. The reduction in 6-4PP lesions may indicate that the mechanism of NAM-PG is better suited for photoprotection than NAM-mono. NAM-mono was superior to NAM-Met, indicating a dose-dependency of NAM's photoprotection. These results highlight a potential for combining photoprotective compounds to enhance photoprotection.","PeriodicalId":3,"journal":{"name":"ACS Applied Electronic Materials","volume":"7 1","pages":""},"PeriodicalIF":4.7000,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"ACS Applied Electronic Materials","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1159/000538445","RegionNum":3,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENGINEERING, ELECTRICAL & ELECTRONIC","Score":null,"Total":0}
引用次数: 0
Abstract
INTRODUCTION
Ultraviolet radiation (UVR) is the primary risk factor for keratinocyte carcinomas (KC). Oral supplementation with nicotinamide (NAM; NAM-mono) is reported to reduce the formation of new KCs. NAM's photoprotection is mediated by enhanced DNA repair. We wanted to explore whether NAM in combination with anti-proliferative (Metformin; Met) or antioxidant (Phloroglucinol; PG) compounds could potentially enhance its photoprotective effects.
METHODS
Hairless mice (C3.Cg-Hrhr/TifBomTac) were treated orally with either a standard dose of NAM monotherapy (600 mg/kg), or NAM (400 mg/kg) combined with Met (200 mg/kg) (NAM-Met) or PG (75 mg/kg) (NAM-PG). Mice were irradiated with 3.5 standard erythema doses of UVR three times per week to induce tumour development. Photoprotective effects were based on i) tumour onset of the first three tumours, ii) skin photodamage, and iii) DNA damage (cyclobutane pyrimidine dimers [CPDs] and pyrimidine-pyrimidone (6-4) photoproducts [6-4PPs]).
RESULTS
All mice treated with NAM demonstrated a delay in tumour onset and reduced tumour burden compared to the UV control group (NAM, NAM-Met, NAM-PG vs. UV control: p ≤ 0.015). NAM-mono and NAM-PG increased time until all three tumours with no difference between them, indicating a similar degree of photoprotection. NAM-mono had no effect on DNA damage compared to the UV control group (p > 0.05), whereas NAM-PG reduced 6-4PP lesions (p < 0.01), but not CPDs (p > 0.05) compared to NAM-mono. NAM-Met delayed the onset of the third tumour compared to the UV control but demonstrated a quicker onset compared to NAM-mono, suggesting inferior photoprotection compared to nicotinamide monotherapy.
CONCLUSION
NAM-PG was as effective in delaying UVR-induced tumour onset as NAM-mono. The reduction in 6-4PP lesions may indicate that the mechanism of NAM-PG is better suited for photoprotection than NAM-mono. NAM-mono was superior to NAM-Met, indicating a dose-dependency of NAM's photoprotection. These results highlight a potential for combining photoprotective compounds to enhance photoprotection.
期刊介绍：
ACS Applied Electronic Materials is an interdisciplinary journal publishing original research covering all aspects of electronic materials. The journal is devoted to reports of new and original experimental and theoretical research of an applied nature that integrate knowledge in the areas of materials science, engineering, optics, physics, and chemistry into important applications of electronic materials. Sample research topics that span the journal's scope are inorganic, organic, ionic and polymeric materials with properties that include conducting, semiconducting, superconducting, insulating, dielectric, magnetic, optoelectronic, piezoelectric, ferroelectric and thermoelectric.
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