Transmission of chromosomal instability after plutonium α-particle irradiation

Abstract

When investigating the biological effects of ionizing radiation on the haemopoietic system, a confounding problem lies in possible differences between the biological effects of sparsely ionizing, low linear energy transfer radiation such as X-, beta- or gamma-rays, and densely ionizing, high linear energy transfer radiation such as alpha-particles. To address this problem we have developed novel techniques for studying haemopoietic cells irradiated with environmentally relevant doses of alpha-particles from a plutonium-238 source. Using a clonogenic culture system, cytogenetic aberrations in individual colonies of haemopoietic cells derived from irradiated stem cells have been studied. Exposure to alpha-particles (but not X-rays) produced a high frequency of non-clonal aberrations in the clonal descendants, compatible with alpha-emitters inducing lesions in stem cells that result in the transmission of chromosomal instability to their progeny. Such unexpected instability may have important implications for radiation leukaemogenesis.

Delayed chromosomal instability induced by DNA damage.

“…The reason(s) for the discrepancy between the two studies is unclear. Kadhim et al (23) looked only at chromosomal aberrations. Such rearrangements are generally transient and result in cell death.…”

“…Some examples are delayed reproductive cell death in cells surviving X irradiation (6-9, 32, 40), delayed mutation in cells exposed to the alkylating agent ethyl methanesulfonate (44) or to X irradiation (7,32,40), and delayed chromosomal instability in cells surviving exposure to ionizing radiation (20,23,26,39). In all cases the cells initially survived exposure to the DNA damage and were capable of reproductive cell proliferation.…”

Heavy ion carcinogenesis and human space exploration

“…For HZE nuclei such a fundamental question is complicated by what are the consequences of the early events that are already known to be different from X-rays (see Figure 3) and do they lead to an alien architecture on the voyage to malignancy? Tissue effects independent of DNA damage that have been associated with cancer initiation or progression include genomic instabilityP [64][65][66][67][68] P, extracellular matrix remodeling [69][70] , persistent inflammation [71][72] , and oxidative damage [73][74] . HZE nuclei will likely modify these responses, along with DNA changes, in ways distinct from other radiation types or carcinogens complicating our ability to estimate and mitigate risks.…”

Applications of amorphous track models in radiation biology

“…Genomic instability refers to the appearance of delayed chromosome abnormalities, mutation or lethality in the progeny of irradiated cells seen with both highand low-LET radiation [70,71]. A recent study using low-energy alpha-particle beams indicates that genomic instability in vitro, as measured by the appearance of delayed chromosome aberrations, is as prevalent in neighbouring cells as in cells that received direct traversals of alpha-particles [72].…”