Age dependency of DNA repair in rats after DNA damage by carcinogens

Damage to DNA seems to be an important cause of cancer and to play a role in aging. Much of this damage results from the action of chemical agents in the environment. These chemicals provide a chance to study DNA repair mechanisms and to construct a model for the investigation of changes in repair with aging. To damage the DNA of male Sprague-Dawley rats aged 6, 22–24 and 24–26 months, three carcinogens were used: N-methyl-N-nitrosourea (MNU), methyl methane sulfonate (MMS) and N,N-dimethylnitrosamine (DMN). DNA repair was measured as unscheduled DNA synthesis (UDS) in ten (MNU and DMN) and five (MMS) different organs. MNU and MMS react with DNA without being first metabolized and show a higher UDS in lower concentration than DMN which is metabolized enzymatically prior to the reaction. This result suggests that MNU and MMS produce more damage in the DNA. There are distinct differences in the spleen, lung, liver, kidney and heart in young animals as well as in the tissues of the kidney and the duodenum in old rats. Clearly we can see a reduction of UDS in the old as compared to the young animals after damage by MNU in the skin, lung, brain and heart, by MMS in the heart and liver, and by DMN in the kidney, duodenum, lung and liver, and by all three mutagens in the spleen and testes. These results confirm those obtained after damaging DNA by means of γ- and UV-irradiation.