DNA damage and repair in children with Down's syndrome

Down's syndrome (DS) is associated with the presence of a third 21 chromosome and is generally considered as a non-cancer-prone genetic disease. However, leukaemias occur more frequently in children with the syndrome than in general population and there is an open question, whether the presence of an additional chromosome may contribute to genomic instability, which, in turn, may play a role in a higher susceptibility to cancer and leukaemias in particular. In order to assess genomic instability associated with the presence of a third 21 chromosome, we determined the level of endogenous DNA damage and susceptibility to a genotoxic stress-inducing factor, hydrogen peroxide and N-methyl-N'-nitro-N-nitrosoguanidyne (MNNG) as well as the ability to remove DNA damage in the peripheral blood lymphocytes of children with DS and healthy kids. The level of DNA damage and the kinetics of DNA repair were evaluated by alkaline comet assay. Oxidative DNA damage was assayed with DNA repair enzymes: endonuclease III-like NTH1 and formamidopyrimidine-DNA glycosylase. The cells taken from children with DS did not display an effective DNA repair after treatment with 10 mM hydrogen peroxide. No difference in the sensitivity to DNA-damaging agents and the efficacy of DNA repair due to age and gender in DS children was observed. These results suggest that children with DS may be characterized by the increased sensitivity to the DNA-damaging agents impaired cellular reaction to DNA damage, which, in turn, may increase the probability of cancers in these children. Therefore, a special care to avoid exposure to potential mutagenic factor my be considered in these children.