Direct DNA damage

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Direct DNA damage: The UV-photon is directly absorbed by the DNA (left). One of the possible reactions from the excited state is the formation of a thymine-thymine cyclobutane dimer (right). The direct DNA damage leads to sunburn and it causes an increases melanin production. Thereby it leads to a long lasting tan. Importantly it is responsible for only 8% of all melanoma.

The distinction between direct DNA damage and indirect DNA damage is highly relevant for the discussion of UV-induced skin damage, the mechanism of photocarcinogenesis (light induced formation of Melanoma) and the effect of sunscreens. The direct DNA damage can occur when DNA directly absorbs the UV-B-photon. It causes sunburn and it triggers the production of melanin.

Due to the excellent photochemical properties of DNA this nature-made molecule is damaged only by a tiny fraction of the absorbed photons. DNA transforms more than 99.9% of the photons into harmless heat (But the damage from the remaining < 0.1% of the photons is still enough to cause sunburn). The transformation of excitation energy into harmless heat occurs via a photochemical process called internal conversion. In DNA this internal conversion is extremely fast - and therefore efficient. This ultrafast internal conversion is an extremely powerful photoprotection for DNA. It has developed 4 billion years ago, when no oxygen and no ozone was present that could have filtered the UV-light. At the dawn of life the intensity of UV-light was 100 to 1000 times stronger than today and as a consequence all molecules that did not possess this natural photoprotection were destroyed and the favourable photochemical properties of all DNA on this planet are a result of this very first evolutionary selection process.[1]

The absorption spectrum of DNA shows a strong absorption for UVB-radiation and a much lower absorption for UVA-radiation. Since the action spectrum of sunburn is identical to the absorption spectrum of DNA, it is generally accepted that the direct DNA damages are the cause of sunburn. While the human body reacts to direct DNA damages with a painful warning signal, no such warning signal is generated from indirect DNA damage, and the indirect DNA damage is responsible for 92% of all melanoma cases.[2]

genetical analysis and the mechanistic cause of melanoma

The direct DNA damage causes mutations which contain a UV-signature (a rather unfortunate name, since the indirect DNA damage can be caused by UV-radiation as well). These UV-signature mutations can be found in only 8% of all melanoma cases.[2]. Most melanoma do not carry a UV-signature mutation and are therefore caused by the indirect DNA damage. Thus it can be said that sunburn (direct DNA damage) is only responsible for a small fraction of all melanoma.

The more widespread use of sunscreen which penetrates into the skin and thereby amplifies the amount of free radicals and oxidative stress [3] is one of the reasons for the increased melanoma rate.

comparison to indirect DNA damage

The direct DNA damage occurs only on locations of the body that are directly exposed to UV-radiation. It leads to the non-lethal forms of skin cancer: basal-cell carcinoma and squamous cell carcinoma. Therefore it should be considered as medically less relevant.

effect of topical sunscreen and effect of absorbed sunscreen

The direct DNA damage is reduced by sunscreen. When the sunscreen is at the surface of the skin it filters the UV-rays which attenuates the intensity. Even when the sunscreen molecules have penetrated into the skin they protect against the direct DNA damage, because the UV-light is absorbed by the sunscreen and not by the DNA.

Please compare to indirect DNA damage.

See also

References

  1. "ultrafast internal conversion of DNA". Retrieved 2008-02-13.
  2. 2.0 2.1 Davies H.; Bignell G. R.; Cox C.; (2002). "Mutations of the BRAF gene in human cancer". Nature. 417: 949–954. Unknown parameter |month= ignored (help)
  3. Hanson Kerry M.; Gratton Enrico; Bardeen Christopher J. (2006). "Sunscreen enhancement of UV-induced reactive oxygen species in the skin". Free Radical Biology and Medicine. 41 (8): 1205–1212.


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