A PCR-based clonal analysis of radiation-induced loss of heterozygosity inhaemopoietic stem cells

CBA mouse strains have been used for many years as a model of radiation-ind uced acute myeloid leukaemia and the leukaemias in CBA and their F1 hybrids are characterised by a specific loss of heterozygosity involving one homol ogue of chromosome 2. Previous cytogenetic studies of transplanted irradiat ed bone marrow, or of bone marrow obtained from irradiated mice significant ly before the appearance of leukaemia, have been interpreted as the chromos ome 2 deletion being a high frequency, possibly initiating event. However t hese studies had not specifically addressed the question oi whether the cha racteristic deletion was induced at a high frequency in stem cells. Using a PCR-based technique, we have studied the induction of chromosome 2 LOH in the progeny of (CBA/H x C57BL/6)F1 stem cells after a potentially leukaemog enic radiation exposure. Whilst chromosome 2 LOH can be induced directly by irradiation and there is a preferential loss of the CBA allele, the freque ncy is no greater than LOH induced in other chromosomal regions studied. Th e data do not support radiation-induced deletion involving one homologue of chromosome 2 in long-term repopulating stem cells (<1 in 200) being as hig h a frequency event as might be inferred by previous cytogenetic studies of total bone marrow.