Effect of cyclosporin A on DNA repair and cancer incidence in kidney transplant recipients

Cancer incidence is enhanced in transplant recipients, Decreased DNA repair ability is associated with increased cancer incidence. Transplanted patien ts with cancer were found to have reduced DNA repair. We hypothesized that immunosuppressive therapy may impair DNA repair and thus contribute to the increased cancer incidence in transplanted patients. The objectives of this study were (1) to investigate the effect of two immunosuppressive treatmen t protocols on DNA repair in kidney transplant recipients; (2) to evaluate the cancer incidence in these patients; and (3) to study the in vitro effec t of cyclosporin A (CsA), azathioprine, and prednisolone-separately and in various combinations-on DNA repair, Three groups were studied: (1) a contro l group; (2) patients treated with azathioprine and prednisone (double-ther apy group); and (3) patients treated with CsA, azathioprine, and prednisone (triple-therapy group). The two patient groups did not differ in age, gend er, time on dialysis before transplantation, or kidney function or in the n umber of acute rejections. However, the interval from transplantation to th e DNA repair study was shorter in the triple-therapy group (P < .01). DNA r epair was induced in peripheral blood mononuclear cells (PBMCs) by ultravio let irradiation and expressed as tritiated thymidine uptake by these cells, DNA repair in the triple-therapy group was 679 +/- 64 cpm/10(6) cells, sig nificantly less than that in the control group (1049 +/- 69 cpm/10(6) cells , P < .02). In the double-therapy group, DNA repair was similar to that in the control group. The follow-up period was shorter in the tripletherapy gr oup (116 +/- 19 months vs 174 +/- 29 months, P < .01), Five tumors develope d in the triple-therapy group, but only one developed in the double-therapy group (P = .05). The in vitro study showed a dose-dependent reduction in P BMC DNA repair by CsA. Azathioprine and prednisolone reduced DNA repair sli ghtly, but CsA reduced DNA repair significantly more than either one or a c ombination of them. In summary, triple therapy was associated with impaired PBMC DNA repair and increased cancer incidence, CsA was responsible in lar ge part for the reduction in DNA repair ability found in the in vitro and i n vivo studies, This may have partly contributed to the enhanced cancer inc idence in the kidney transplant recipients.