Definitions

# Indirect DNA damage

Indirect DNA damage occurs when a UV-photon is absorbed in the human skin by a chromophore that does not have the ability to convert the energy into harmless heat very quickly. Molecules which do not have this ability have a long lived excited state. This long lifetime leads to a high probability for reactions with other molecules - so called bimolecular reactions. Melanin and DNA have extremely short excited state lifetimes in the range of a few femtoseconds (10-15s) . The excited state lifetime of these substances is 1,000 to 1,000,000 times longer than the lifetime of melanin and therefore they may cause damage to living cells which come into contact with them.

The molecule which originally absorbs the UV-photon is called a "chromophore". The bimolecular reactions can either occur between the excited chromophore and DNA, or between the excited chromophore and another species to produce free radicals and Reactive Oxygen Species. These reactive chemical species can reach DNA by diffusion and the bimolecular reaction will damage the DNA (oxidative stress). Importantly, indirect DNA damage does not result in any warning signal or pain in the human body.

The mutations which result from direct DNA damage and those which result from indirect DNA damage are different, and genetic analysis of melanomas can elucidate which DNA damage has caused each respective skin cancer. Studies using these techniques have found that 92% of all melanoma are caused by indirect DNA damage and only 8% of the melanoma are caused by direct DNA damage.

The bimolecular reactions that cause the indirect DNA damage are illustrated in the figure:

$mathrm\left\{\left(Chromophore\right)^* + \left\{\right\}^3O_2 xrightarrow\left\{\right\} Chromophore + \left\{\right\}^1O_2\right\}$
1O2 is reactive harmful singlet oxygen:
$mathrm\left\{\left\{\right\}^1O_2 + intact DNA xrightarrow\left\{\right\} \left\{\right\}^3O_2 + damaged DNA\right\}$

## Location of the damage

Direct DNA damage is confined to areas that can be reached by UV-B light. In contrast free radicals can travel through the body and affect other areas - possibly even inner organs. The traveling nature of the indirect DNA damage can be seen in the fact that the malignant melanoma can occur in places that are not directly illuminated by the sun - this is in contrast to basal-cell carcinoma and squamous cell carcinoma which only appear on directly illuminated locations of the body.

## Effects of topical vs. absorbed sunscreen

Indirect DNA damage is reduced by the topical sunscreen that stays on the surface of the skin. However, if sunscreen penetrates the epidermal barrier and gets into contact with living tissue, the indirect DNA damage is amplified many times, which causes damage to living tissue even at very low concentrations (10 μmol/L).