POSTIRRADIATION GROWTH IN HAT MEDIUM FAILS TO ELIMINATE THE DELAYED APPEARANCE OF 6-THIOGUANINE-RESISTANT CLONES IN EJ30 HUMAN EPITHELIAL-CELLS

The latent effects of radiation-induced damage include ''delayed'' mut ations that arise de novo in the progeny of nonmutant cells. We invest igated the early stages of delayed mutagenesis at the HPRT locus of EJ 30 human epithelial cells that were exposed to 4 Gy of Cs-137 gamma ra ys. To eliminate directly induced ''prompt'' HPRT- mutants, cultures w ere grown in HAT medium before selection in 6-thioguanine was applied. Although irradiated cells were grown in HAT medium throughout the phe notypic expression period, mutant fractions some tenfold above spontan eous levels were observed subsequently; incubation in HAT medium did n ot cause an increase in mutations in unirradiated cells. We conclude t hat, in our experimental system, a significant proportion of induced m utation is of a delayed type. We speculate that the delayed induction is caused by an instability process that is a frequent and (typically) transient consequence of exposure of cells to ionizing radiation. The connection, if any, between this process and other manifestations of instability, including the acquisition of a ''mutator phenotype,'' rem ains to be established. (C) 1998 by Radiation Research Society.