Clinical trial NCT00864955: Cutaneous DNA Damage Caused by UV-A Irradiation
Official title: Damage to DNA Caused by UV-A Irradiation: Photochemical Mechanism and Cutaneous Parameters Involved in the Formation of Cyclobutane Pyrimidine Dimers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Healthy Volunteers
Keywords: UV-A irradiation
Cyclobutane-Pyrimidine Dimer
Oxidative lesions
cutaneous phototype
UV-B irradiation
DNA damages
Lead sponsor: University Hospital, Grenoble
Sponsor class: OTHER
Collaborators: name: Commissariat A L'energie Atomique
First posted: 2009-03-19
Enrollment: 24
Sex: MALE
Minimum age (years): 18
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: HEALTH_SERVICES_RESEARCH

Brief summary: The DIMUVA study aims to evaluate the correlation between cutaneous phototype and the nature and quantity of damage caused to cutaneous DNA after exposure to UV-A radiation.

Detailed description: Due to their capacity to damage Deoxyribonucleic acid (DNA), Ultra-Violet (UV) radiation is one of the causes of skin cancers.

Until recently, the genotoxic effects of UV-A radiation, were poorly identified, in particular their capacity to lead to the dimerization of pyrimidine bases .

It is well known that the response to UV-A and UV-B radiations is different depending on the cutaneous phototype.

Thus, the aim of this study is to determine the correlation between cutaneous phototype and the quantity and nature (CPD or oxidative lesions) of damage caused to cutaneous DNA after an ex-vivo exposure to UV-A and UV-B radiations.

Eligibility criteria: Inclusion Criteria:

* Male,
* Between 18 and 35 years old,
* Healthy volunteers,
* Cutaneous phototype 2 or 4 according to the Fitzpatrick classification,
* Affiliation to the French Social Security.

Exclusion Criteria:

* History of photosensibility,
* Active smoking or stopped since less than one year,
* Dermatological pathology or treatment contra-indicating cutaneous irradiation and skin biopsies,
* Any chronic pathology susceptible to interfere with the evaluations related to the protocol,
* Allergy to local anaesthetics,
* Volunteers who take drugs and/or food complements acting on oxidative stress in the 8 weeks preceding inclusion,
* Volunteers who have take paracetamol or aspirin within 7 days prior to the inclusion visit,
* Subject in exclusion period for another biomedical research study,
* Subject having exceeded the threshold of annual compensation for biomedical research.

Primary outcomes:
measure: Phototype determination according to the Fitzpatrick classification Number of CPD and oxidative lesions determinated by the analysis of DNA from the skin biopsies after their ex-vivo exposure to UV-A - The CPD / Oxidative lesions ratio
timeFrame: Day 0
Secondary outcomes:
measure: Number of CPD and oxidative lesions determinated by the analysis of DNA from the skin biopsies after their exposure ex-vivo to UV-B.
timeFrame: Day 0
measure: UV-A radiation exposure: Minimal erythemic dose - Number of CPD and oxidative lesions - CPD / oxidative lesions ratio
timeFrame: Day x
measure: UV-B radiation exposure: Minimal erythemic dose - Number of CPD and oxidative lesions - CPD/oxidative lesions ratio
timeFrame: Day 0
measure: antioxidant status and quantity of CPD, oxidative lesions after exposure to UV-A and UV-B radiations
timeFrame: day 2
Other outcomes:
Locations:
city: Grenoble
country: France
facility: Centre d'investigation Clinique ,University Hospital Grenoble
city: Grenoble
country: France
facility: Department of Dermatology, University Hospital Grenoble
Study officials:
affiliation: University Hospital, Grenoble
name: Jean-Claude BEANI, Pr
role: PRINCIPAL_INVESTIGATOR
References:
citation: Brash DE. Sunlight and the onset of skin cancer. Trends Genet. 1997 Oct;13(10):410-4. doi: 10.1016/s0168-9525(97)01246-8.
citation: Melnikova VO, Ananthaswamy HN. Cellular and molecular events leading to the development of skin cancer. Mutat Res. 2005 Apr 1;571(1-2):91-106. doi: 10.1016/j.mrfmmm.2004.11.015.
citation: Cadet J, Sage E, Douki T. Ultraviolet radiation-mediated damage to cellular DNA. Mutat Res. 2005 Apr 1;571(1-2):3-17. doi: 10.1016/j.mrfmmm.2004.09.012. Epub 2005 Jan 26.
citation: Douki T, Reynaud-Angelin A, Cadet J, Sage E. Bipyrimidine photoproducts rather than oxidative lesions are the main type of DNA damage involved in the genotoxic effect of solar UVA radiation. Biochemistry. 2003 Aug 5;42(30):9221-6. doi: 10.1021/bi034593c.
citation: Dumaz N, Drougard C, Sarasin A, Daya-Grosjean L. Specific UV-induced mutation spectrum in the p53 gene of skin tumors from DNA-repair-deficient xeroderma pigmentosum patients. Proc Natl Acad Sci U S A. 1993 Nov 15;90(22):10529-33. doi: 10.1073/pnas.90.22.10529.