Quantification of DNA Repair Products in the Urine After Ultraviolet Radiation of the Skin

NCT05277961 | Unknown

• 1 other identifier: H-20076172
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

Purpose of the experiment The investigators know that DNA damage is formed in the skin by sun exposure of the thymine-dimer type. Many of these injuries are repaired and excreted through the urine. The purpose of the study is to quantify DNA damage in the urine after ultraviolet (UV) irradiation of the skin in healthy subjects. The investigators would like to investigate which day after two different irradiation regimens the highest secretion of thymine dimers occurs. If the investigators establish such a test system, it will be possible to test potential photoprotective substances or potential photocarcinogenic substances. Method of the experiment, design, and examination procedures The subjects (n = 16-20) are recruited by a post on Bispebjerg's hospital website. Based on this, subjects are divided into 2 groups of 8-10 people. Group 1 is irradiated 3 times with 1 standard erythema dose (SED). 1 SED corresponds to approx. 10 minutes sun around 13 pm on a good Danish summer day. Group 2 is irradiated once with 3 SED, which corresponds to approx. 30 minutes around 13 pm on a good Danish summer day. The irradiation is carried out on day 1 for group 2 and days 1, 2 and 3 for group 1. Subjects are irradiated in a full-body UV cabin (Waldmann, Willing-Schwenningen, Germany) with 26 F85 / 100W UV6 tubes (290-350 nm, broad-spectrum). 13 seconds of illumination, equivalent to 1 SED. The subjects are standing in the cabin and have a screen on so that their eyes and face are not exposed to radiation. When irradiated, the subjects must only wear underwear, which for men are underpants/boxer shorts, while for women it is bras and panties. The experiment is performed between October and March, to avoid that the subjects do not simultaneously receive UV radiation from the sun and thus form DNA damage. Subjects must collect morning urine in dispensed containers and must store it in their own freezer until the final visit. Morning urine (2x 50 mL) is collected before irradiation, called day 1, and even until day 8 after the last exposure, ie. day 10 for group 1 and day 8 for group 2. Before the first exposure, pigment and redness are measured on the subjects. Pigment and redness measurements are performed on the back, chest, and shoulder.

Conditions

Ultraviolet Rays; Injury; DNA Adduct Formation; DNA Damage, Radiation Induced; DNA Damage

Keywords

DNA repair; DNA damage; Thymine dimer; Ultraviolet radiation; Urine; HPLC-MS

Outcome Measures

Primary Outcomes (1)

• Determination of days where the concentration of excreted thymine dimers (a marker of DNA damage) is the highest in the urine after UVR exposure of the skin.

  Each participant of group 1 will provide a total of 1000 ml (2 x50 ml x10 days) of urine and participants of group 2 will provide a total of 800 ml (2 x 50 ml x 8 days) of urine at the end of the experiment. UVR induced thymine dimers repaired and excreted in the urine will be quantified (by Ultra High-pressure Liquid Chromatography-Mass Spectrometry (UHPLC-MS) from urine collected before and after irradiation regimes. The highest concentration of thymine dimers in urine will indicate the most optimal time for urine collection after irradiation.

  10 days

Study Arms (2)

UVR Dose 1x3SED

EXPERIMENTAL

UVR Dose 1x3 standard erytheme dose (SED)

Radiation: Ultraviolet radiation

UVR dose 3x1SED

EXPERIMENTAL

UVR dose 3x1 standard erythema dose (SED)

Radiation: Ultraviolet radiation

Interventions

Ultraviolet radiation RADIATION

UV6 tubes

UVR Dose 1x3SED; UVR dose 3x1SED

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Over the age of 18
• Written informed consent from the subject

You may not qualify if:

• Immunosuppressed individuals
• Sun holiday/ski holiday/solarium 4 weeks before the trial starts
• Skin disease
• Medicines that cause photosensitivity or affect DNA repair
• Pregnancy

Sponsors & Collaborators

• Bispebjerg Hospital: lead
• Sygehus Lillebaelt: collaborator

Study Sites (1)

Bispebjerg Hospital, Department of Dermatology

Copenhagen NV, DK-2400, Denmark

Location

Related Publications (4)

• Brash DE, Rudolph JA, Simon JA, Lin A, McKenna GJ, Baden HP, Halperin AJ, Ponten J. A role for sunlight in skin cancer: UV-induced p53 mutations in squamous cell carcinoma. Proc Natl Acad Sci U S A. 1991 Nov 15;88(22):10124-8. doi: 10.1073/pnas.88.22.10124.

  PMID: 1946433 BACKGROUND

• Martens MC, Emmert S, Boeckmann L. Sunlight, Vitamin D, and Xeroderma Pigmentosum. Adv Exp Med Biol. 2020;1268:319-331. doi: 10.1007/978-3-030-46227-7_16.

  PMID: 32918226 BACKGROUND

• Le Curieux F, Hemminki K. Cyclobutane thymidine dimers are present in human urine following sun exposure: quantitation using 32P-postlabeling and high-performance liquid chromatography. J Invest Dermatol. 2001 Aug;117(2):263-8. doi: 10.1046/j.1523-1747.2001.01416.x.

  PMID: 11511303 BACKGROUND

• Petersen B, Wulf HC, Triguero-Mas M, Philipsen PA, Thieden E, Olsen P, Heydenreich J, Dadvand P, Basagana X, Liljendahl TS, Harrison GI, Segerback D, Schmalwieser AW, Young AR, Nieuwenhuijsen MJ. Sun and ski holidays improve vitamin D status, but are associated with high levels of DNA damage. J Invest Dermatol. 2014 Nov;134(11):2806-2813. doi: 10.1038/jid.2014.223. Epub 2014 May 20.

  PMID: 24844860 BACKGROUND

MeSH Terms

Conditions

Wounds and Injuries

Interventions

Ultraviolet Rays

Intervention Hierarchy (Ancestors)

Light; Electromagnetic Radiation; Electromagnetic Phenomena; Magnetic Phenomena; Physical Phenomena; Optical Phenomena; Radiation; Radiation, Ionizing; Radiation, Nonionizing; Sunlight; Weather; Atmosphere; Environment; Ecological and Environmental Phenomena; Biological Phenomena; Meteorological Concepts; Environment and Public Health

Study Officials

• Hans Christian Wulf, PhD

  RegionH

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Model Details: Two groups of healthy volunteers are UV radiated with two different dosage regimen. DNA repair excreted in the urine are quantified by LC-MS

Study Record Dates

• First Submitted: February 17, 2022
• First Posted: March 14, 2022
• Study Start: March 1, 2022
• Primary Completion: February 1, 2024
• Study Completion: March 1, 2025
• Last Updated: October 12, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)