UVA-induced cyclobutane pyrimidine dimers in DNA: a direct photochemical mechanism?

Abstract

The carcinogenic action of UVA radiation is commonly attributed to DNA oxidation mediated by endogenous photosensitisers. Yet, it was recently shown that cyclobutane pyrimidine dimers (CPD), well known for their involvement in UVB genotoxicity, are produced in larger yield than oxidative lesions in UVA-irradiated cells and skin. In the present work, we gathered mechanistic information on this photoreaction by comparing formation of all possible bipyrimidine photoproducts upon UVA irradiation of cells, purified genomic DNA and dA(20):dT(20) oligonucleotide duplex. We observed that the distribution of photoproducts, characterized by the sole formation of CPD and the absence of (6-4) photoproducts was similar in the three types of samples. The CPD involving two thymines represented 90% of the amount of photoproducts. Moreover, the yields of formation of the DNA lesions were similar in cells and isolated DNA. In addition, the effect of the wavelength of the incident photons was found to be the same in isolated DNA and cells. This set of data shows that UVA-induced cyclobutane pyrimidine dimers are formed via a direct photochemical mechanism, without mediation of a cellular photosensitiser. This is possible because the double-stranded structure increases the capacity of DNA bases to absorb UVA photons, as evidenced in the case of the oligomer dA(20):dT(20). These results emphasize the need to consider UVA in the carcinogenic effects of sunlight. An efficient photoprotection is needed that can only be complete by completely blocking incident photons, rather than by systemic approaches such as antioxidant supplementation.

Photoinduced Damage to Cellular DNA: Direct and Photosensitized Reactions†

“…It may be added, although being a much lower process than in the UVC and UVB ranges, that absorption of UVA photons by DNA is a well-documented fact (94) that was recently shown to be driven by the stacking of bases in the double helix (95,96). Comparative experiments showed that the yields of UVA-induced CPDs were similar in isolated and cellular DNA (55,96,97). This suggests that endogenous sensitizers play at best a minor role in the formation of these photoproducts.…”

18-årsgrensen for solariebruk skal håndheves

“…A recent publication (Mouret et al, 2010) reported the important finding that a UVAtriggered chemical excitation of melanin derivatives induces DNA photoproducts (CPDs) long after UVA exposure (> 3 hours). These "dark CPD" constitute the majority of CPDs that initiate UV-signature mutations in melanocytes derived from mice and in mice skin.…”

Photochemistry of 1,3-Dicarbonyl Compounds: DNA Photodamage vs. Photoprotection

“…[50] UVA irradiations performed in more complex systems such as calf thymus DNA and keratinocytes samples, where an extreme caution was made to avoid the presence of photosensitizer, have revealed that the only photoproducts observed are TT, TC and CT CPDs (TT > TC > CT). [50] These experiments have shown that the UVA carcinogenic potential was underestimated and this recent discovery claims for a complete blocking of the incident photons by the use of photoprotection.…”

“…In this way, high SPFs provide more protection against the dangerous effects of sunlight than low SPF. In the European Union sunscreens are classified according to their SPF into low (SPF 6, 10), medium (SPF 15,20,25), high (SPF 30,50), and very high (SPF 50+). [71] SPF = MED of protected skin / MED of unprotected skin eq.…”