A DNA Repair Complex to Decrease Erythema and UV-induced CPD Formation

May 1, 2008 | Contact Author | By: Giorgio Dell’Acqua, Dellacqua Consulting and Kuno Schweikert, Induchem AG
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Title: A DNA Repair Complex to Decrease Erythema and UV-induced CPD Formation
UVx DNA repairx cyclobutane pyrimidine dimerx prolinex tyrosinex erythemax
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Keywords: UV | DNA repair | cyclobutane pyrimidine dimer | proline | tyrosine | erythema

Abstract: The authors describe how a DNA-repair complex based on amino acids decreases UV-induced DNA damage in reconstituted human skin and reduces related skin inflammation in human volunteers.

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Solar radiation such as UVA and UVB induces physiological damage in the skin. Photoaging is a classic example of UV-induced wrinkle formation and thinning of the skin. This phenotype change reflects a deeper impact at the molecular level, in particular on the DNA double helix present in each cell nucleus. The cumulative effect of repeated damage strongly contributes to the development of DNA mutations and down-regulates proteins essential to maintain normal skin turnover.

Prominent among UV-induced lesions on DNA are cyclobutane pyrimidine dimers (CPDs) formed between adjacent pyrimidines on the same DNA strand exposed to UVB (280–320 nm) irradiation. Pyrimidine dimers alter the biological function of DNA and are a major cause of lethal, transformational and tumorigenic4 events induced by UV exposure. UV-induced CPDs may be repaired by enzymatic processes, or by a light-dependent reaction mediated by electron transfer. Importantly, the repairing mechanism decreases with aging, contributing to increased mutational risk.

Furthermore, studies in cell lines and in animals have demonstrated a link between DNA damage and erythema formation. Mediators of inflammation such as NF-kB, IL-6, IL-10 and TNF-α were induced by CPDs, and the reduction of these inflammatory mediators was stimulated by mechanisms that increase CPD repair. In vivo studies on animals such as knockout and transgenic mice further proved that when enzymes essential to DNA repair were over-expressed or deleted, a clear correlation with the onset of UV-induced skin erythema was evidenced.

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Figure 1. Environmental aggressions

Figure 1. Environmental aggressions

Figure 2. Amino acids

Figure 2. Amino acids 

Figure 3. Time table of the reconstituted human skin

 Figure 3. Time table of the reconstituted human skin

Figure 4. Time table of the experiment on the inner forearms

 Figure 4. Time table of the experiment on the inner forearms

Figure 5. Reduction of number and intensity

 Figure 5. Reduction of number and intensity

Figure 6. 20 min pretreatment

 Figure 6. 20 min pretreatment 

Figure 7. Skin redness in human volunteers

Figure 7. Skin redness in human volunteers 

Dell’Acqua: A DNA Repair footnotes

 a Unirepair T-43 (INCI: Acetyl tyrosine (and) proline (and) hydrolyzed vegetable protein (and) adenosine triphosphate) is a product of Induchem.

b 0.5 cm2, aged day 17, Skinethic, France

c 1:400, Anti-Thymine Dimer, clone KTM53, mouse IgG, Kamiya Biomedical Company, Seattle, Washington, USA

d DAKO Diagnostika GmbH, Hamburg, Germany. DAKO is a registered trade name

e DAKO Diagnostika GmbH, Hamburg, Germany

f Olympus CK40 microscope, 400x magnification.

g Microscope: DXC-950 OP, Olympus; Video documentation: Sony Deutschland GmbH

h Eubos flüssig – blau, manufactured by Dr. Hobein, Meckenheim-Merl, Germany. Eubos is a registered trade name.

k Solar Light Model 601-300 Multiport
 
m Chromameter CR 400, Minolta, Japan

Formula 1. Cream used

 Formula 1. Cream used

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