Long-term in vivo transmission of alpha-particle-induced chromosomal instability in murine haemopoietic cells

Abstract

We have previously reported non-clonal cytogenetic aberrations in the clonal descendants of murine haemopoietic stem cells irradiated in vitro with alpha-particles. The data are consistent with a transmissible chromosomal instability induced in a stem cell resulting in a diversity of aberrations in its clonal progeny many cell divisions later. To determine whether this instability is transmissible in vivo, bone marrow cells obtained from the male mouse have been irradiated with alpha-particles in vitro and transplanted into female recipients. In the repopulated haemopoietic system we have observed persisting chromosomal instability up to 1 year post-transplantation. The findings demonstrate a long-lived effect of the alpha-particle-induced lesion in the donor repopulating stem cells.

Chromosome analysis in childhood cancer survivors and their offspring—No evidence for radiotherapy-induced persistent genomic instability

“…Studies of mice irradiated in utero have provided conflicting results [11][12][13] although it is difficult to make comparisons because of differences in exposure regimes, cellular systems examined and cytogenetic endpoints. Cytogenetic studies suggesting that radiation-induced genomic instability could be transmitted in vivo in ablated mice transplanted with in vitro irradiated bone marrow [7,14] could not be confirmed [15] with this latter study also failing to find evidence of chromosomal instability in bone marrow cells following in vivo irradiation. Preliminary results from an on-going mouse study involving sequential sampling of polychromatic erythrocytes following whole-body irradiation have also failed to find an effect [16].…”

Particulate debris from a titanium metal prosthesis induces genomic instability in primary human fibroblast cells

“…Characteristically, it is induced at frequencies greater than that of natural spontaneous mutations (Kadhim et al, 1996). Once induced, genomic instability is effectively permanent and has been shown to persist in vitro and in vivo for many cell doublings (Seymour et al, 1986;O'Reilly et al, 1994;Watson et al, 1996). The phenomenon of aneuploidy and its relevance to the genetic instability of cancer cells has recently been documented (Duesberg et al, 1998).…”

Comments on the Paper by Wickliffeet al.(Radiat. Res.159, 458–464, 2003)

“…Chromosomal instability in bone marrow cells was also found to be transmissible in vivo by transplanting male cells irradiated with ␣ particles into female recipients (103,104). The repopulated hemopoietic system showed instability that persisted for up to 1 year.…”