And lets not forget endogenous causes!
A) the genotype.
DNA damage will happen regardless of any precautions, this is a fact of life.
Some people have a very efficient DNA repair system, others do not.
B) even if people have efficient repair systems (there are many) that does not guarantee that a damaged DNA in a critical location gets caught in time before it is harmful. It is a chance event and in many ways like russian roulette. All you can do is lower the chances for damage and increase the efficiency of repair systems but the risk will not be zero.
To get an idea for just one type of mutagenic damage. 8-oxoG is a damaged G base that we do not have normally in our DNA. If memory serves my right it was shown that we make and exise gram amounts of this stuff each day. Assume it is just one gram and that each 8-oxoG comes from a damaged DNA segment that means that there were about 10^21 damage events per day. That is 10'000'000 events for each (average) cell/day. These very rough estimate are nevertheless staggering.... and this is just one type of damage!
M
