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Radioadaptation to the Mutagenic Effect of Ionizing Radiation in Human Lymphoblasts: Molecular Analysis of HPRT Mutants¹

Institut Curie-Biologie, 26 rue d'Ulm, 75231 Paris cedex 05, France [O. R., E. M.], and Institute de Protection et de Sureté Nucléaire, Departement de Protection de la Sauté l'Homme et de la Dosimétrie/Section Autonome de Radiobiologie Appliquée à la Medicine-Commissiariat à l'Energie Atomique, Postal Box 6F, 92265 Fontenay-aux-Roses cedex, France [O. R.]

A 70% reduction of HPRT^- mutant frequency in radioadapted human lymphoblastoid cells has been reported, as analyzed by the Southern blot method (O. Rigaud et al., Radiat. Res., 133: 94–101, 1993). The data reported here extend the previous molecular analysis to a collection of 118 mutants. Structural rearrangements of the HPRT gene were determined using the multiplex polymerase chain reaction assay. This allows us to define more precisely the deleted exons in mutants and to ensure the absence of small alterations in exons among mutants with no detectable change after Southern analysis. The phenotype of these latter mutants is likely to be due to point mutations. Overall results of both Southern and multiplex polymerase chain reaction analyses confirm that the proportion of deletion-type mutations is decreased in adapted cells (42%) compared to that in mutants treated with the high dose alone (77%). Mutants with no change at the HPRT gene level were further characterized with respect to their HPRT gene expression. The vast majority of adapted mutants (86%) were still expressing mRNA, whereas HPRT transcripts were detected in only 56% of the mutants induced by the high dose alone. From these data and those reported by others, possible mechanisms underlying the adaptive response are proposed.