Delayed appearance of radiation-induced mutations at the Hprt locus in murine hemopoietic cells.
Earlier work in this laboratory identified high levels of non-clonal chromatid aberrations in the clonal descendants of murine hemopoietic stem cells after many cell divisions postirradiation with densely-ionizing, high linear energy transfer (LET) alpha-particles, but not with sparsely ionizing low LET X-rays. Using the Hprt locus as a marker, we have now demonstrated genomic instability in murine hemopoietic stem cells for greater than 20 cell divisions following both high and low LET irradiation. The increase in Hprt-deficient variants demonstrated following X- as well as alpha-particle and neutron irradiation indicates that there is a difference in the LET-dependence of delayed gene mutations and higher-order cytogenetic effects. Over 90% of the mutations identified arose in the expanding colonies after more than 12 cell divisions postirradiation and therefore cannot be attributed to the initial DNA damage. Such a high frequency of delayed mutations has important implications for mechanistic studies of radiation mutagenesis and for risk estimation.
Harper
K
K
Medical Research Council-Radiation and Genome Stability Unit, Chilton, Didcot, Oxon., UK.
Lorimore
S A
SA
Wright
E G
EG
D000512:Alpha Particles; D000818:Animals; D001853:Bone Marrow / Q000528:radiation effects; D001854:Bone Marrow Cells; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D006410:Hematopoiesis / Q000528:radiation effects; D006412:Hematopoietic Stem Cells / Q000528:radiation effects*; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics*; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D016296:Mutagenesis / Q000528:radiation effects*; D009154:Mutation; D009502:Neutrons; D013997:Time Factors; D014965:X-Rays
D007041:Hypoxanthine Phosphoribosyltransferase