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:
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