DEFECTIVE G2 REPAIR IN DOWN-SYNDROME - EFFECT OF CAFFEINE, ADENOSINE AND NIACINAMIDE IN CONTROL AND X-RAY-IRRADIATED LYMPHOCYTES

Lymphocytes from both Down syndrome (DS) patients and age-matched cont rol donors have been investigated to identify a possible disturbance i n chromosomal G2 repair. Analyses of caffeine treatments during G2 hav e shown that the frequency of chromosomal aberrations is higher in DS lymphocytes than in normal lymphocytes. Likewise, G2 duration is longe r in DS cells than in normal cells. In both control and DS lymphocytes , caffeine treatments increase the frequencies of chromatid breakages and decrease the average of G2 duration. The reversal of the caffeine potentiation effect by adenosine and niacinamide is higher in DS cells than in normal cells. Furthermore, ATP content per cell in DS lymphoc ytes is one third of that estimated in normal lymphocytes. The increas e of ATP level produced by adenosine or niacinamide generally correlat es with the reversal of the caffeine effect on chromosome aberrations. Under the experimental conditions tested, a good negative exponential correlation between ATP level and chromosome aberrations has been det ected in both normal and DS lymphocytes which were or were not X-irrad iated. Finally, we postulate a decrease in G2 repair capability of DS lymphocytes caused by a low availability of ATP and/or some other fact or correlating with it.