Biomonitoring of genotoxic damage in children with chronic renal disease and in those after kidney transplantation

Chronic renal disease is a serious illness that causes severe and irrevesible reduction in kidney function. One consequence of chronic renal disease is an elevated cancer risk. It has been suggested that cancer risk may be related to an elevated level of genomic damage. There has been no previous study examining genomic damage in children with chronic renal disease.We evaluated the genomic damage by using Comet, modified Comet, MN, FISH-MN Assay in lymphocytes, MN Assay in buccal epitelium. Lymphocytes and buccal epitelium were taken from 17 PreD, 15 HD, and 17 Tx pediatric patients. We evaluated the relation between genotoxicity parameters and the measured biochemical parameters. Our control group consist of 20 healthy children who were age and sex matched. The DNA base damage determined by Comet Assay increased in Tx, HD and PreD groups. It was found that purine base damage in PreD and Tx groups was higher than the HD group whereas primidine base damage was the same in all patient groups. MN frequencies in lymphocytes were significantly higher in Tx, HD and PreD groups when compared with that of control. However, the DNA damage as MN frequencies in HD and PreD groups were higher than the Tx group. It has been found that role of both aneugenic and clastogenic mechanisms were evident in increased MN frequencies of all patient groups. However, aneugenic effects were more predominant in HD group. In buccal epithelium, the DNA damage determined by MN Assay was also increased in Tx, HD and PreD groups. There was an interaction between BUN, creatinine, TAS, uric acid, ferritine and genotoxicity parameters analyzed. Regression analysis shows that being in any of the patient groups increases the Comet as DNA base damage , MN, C(+)MN, C(-)MN and buccal MN frequencies. Our results indicate that buccal cells and lymphocytes may complement each other in the detection of a wide range of genotoxic effects in completely different biological targets.In conclusion, our results reveal that pediatric PreD, HD and Tx patients with chronic renal disease have an increased genotoxic damage and thus contributing to the future cancer risk.