DNA-Repair Capacity in Down's Syndrome

Down's syndrome (DS) is the most common chromosomal abnormality in human. Subjects with DS are known to be peridisposed to develop leukemia. The molecular basis of the association between DS and leukemia is unknown. The unscheduled DNA synthesis (UDS) test measure the ability of DNA-repair in mammalian cells after excision of a stretch of DNA containing the region of damage induced by chemical or physical agents. To get further insight into the cause(s) of leukemia in DS, the induction of UDS, in human peripheral blood lymphocytes was determined using hydroquinone and ethidium bromide, as DNA-damaging agents. Peripheral lymphocytes were obtained from 14 patients (7 males, 7 females) and 14 healthy sex- and age-matched normal subjects. The mean of UDS observed in control lymphocytes when treated with hydroquinone and ethidium bromide were 1.69 + 0.65, and 1.10 + 0.29, respectively, and corresponding values for DS lymphocytes were 1.11 + 0.40 and 0.92 + 0.26, respectively. Our results revealed that the lymphocytes of DS patients, showed a decrease in the UDS level. These data suggest that the low capacity of DNA-repair in conjunction with hypersensitivity of DNA and chromosomes of DS patients after treatment with mutagens may be relevant to the high incidence of leukemia in DS patients.