ANALYSIS OF HPRT GENE MUTATION FOLLOWING ANTICANCER TREATMENT IN PEDIATRIC-PATIENTS WITH ACUTE-LEUKEMIA

We evaluated the genotoxic effect of cancer therapy on somatic cell mu tation by isolating 6-thioguanine-resistant mutants in peripheral lymp hocytes. The study population comprised 45 children with acute lymphob lastic leukemia (ALL), 13 children with acute myelogenous leukemia (AM L) and 28 age-matched healthy controls. The geometric mean mutant freq uency for ALL patients was 7.8 x 10(-6), which was significantly highe r than that for AML patients (1.7 x 10(-6)) or for healthy controls (1 .1 x 10(-6)). Fifteen patients with ALL showed a high mutant frequency above 10 x 10(-6), although 10 of them had completed their treatment at least 24 months earlier. Moreover, repeated measurements of mutant frequency at intervals of 12 or more months revealed that the values w ere very stable. Structural hypoxanthine-guanine phosphoribosyl transf erase (hprt) gene alterations, as determined by Southern blot analysis , were seen in 23% (12/52) of mutant clones derived from ALL patients, but not in those from the controls. These results suggest that intens ive anti-cancer therapy of children may produce persistent somatic mut ations, which could be related to the appearance of second neoplasms.