Tracing radiation induced genomic instabilityin vivoin the haemopoietic cells from fetus to adult mouse

Abstract

The present experiment was aimed at studying the delayed expression of fetal irradiation induced genomic instability in the mouse haemopoietic cells in vivo. The abdominal area of 14 day pregnant Swiss albino mice was exposed to 0-1.5 Gy of gamma radiation. Chromosomal aberrations were studied in three passages of spleen colonies (short-term repopulating stem cells, STRSC) derived from 24 h post-irradiation fetal liver cells and in the 1-20 months postpartum bone marrow (long-term repopulating stem cells, LTRSC). Irradiation produced a significant and dose-dependent increase in the aberrant metaphases in the first passage spleen colony (CFU-S1) cells, which decreased in subsequent passages and reached normal levels by the third passage (CFU-S3). Bone marrow at 1-6 months postpartum showed similar chromosomal picture in the 0 Gy control and after 0.5-1.5 Gy, but there was a clear increase in aberrant cells from 9 months postpartum in the irradiated groups. Some mice in all irradiated groups showed a 2.5- to 5-fold increase in peripheral leukocyte counts. Bone marrow of these animals exhibited severe aneuploidy, the chromosome number ranging from less than 1n to 6n at 20 months of age. Our results indicate that unstable chromosome aberrations induced in the fetal haemopoietic STRSC are eliminated during subsequent cell divisions. However, genomic instability induced in the LTRSC persists and is expressed as chromosomal aberrations at advanced ages. Induction of chromosome aneuploidy could be an early step in the chain of events leading to adult leukaemia after prenatal irradiation.