title: Genomic instability, bystander effect, cytoplasmic irradiation and other phenomena that may achieve fame without fortune.
abstract: The possible risk of induced malignancies in astronauts, as a consequence of the radiation environment in space, is a factor of concern for long term missions. Cancer risk estimates for high doses of low LET radiation are available from the epidemiological studies of the A-bomb survivors. Cancer risks at lower doses cannot be detected in epidemiological studies and must be inferred by extrapolation from the high dose risks. The standard setting bodies, such as the ICRP recommend a linear, no-threshold extrapolation of risks from high to low doses, but this is controversial. A study of mechanisms of carcinogenesis may shed some light on the validity of a linear extrapolation. The multi-step nature of carcinogenesis suggests that the role of radiation may be to induce a mutation leading to a mutator phenotype. High energy Fe ions, such as those encountered in space are highly effective in inducing genomic instability. Experiments involving the single particle microbeam have demonstrated a "bystander effect", ie a biological effect in cells not themselves hit, but in close proximity to those that are, as well as the induction of mutations in cells where only the cytoplasm, and not the nucleus, have been traversed by a charged particle. These recent experiments cast doubt on the validity of a simple linear extrapolation, but the data are so far fragmentary and conflicting. More studies are necessary. While mechanistic studies cannot replace epidemiology as a source of quantitative risk estimates, they may shed some light on the shape of the dose response relationship and therefore on the limitations of a linear extrapolation to low doses.
authors.affiliation: Center for Radiological Research and Comprehensive Cancer Center, Columbia University College of Physicians & Surgeons, New York, NY, USA.
authors.forename: E J
authors.initials: EJ
authors.lastname: Hall
mesh_terms: D000512:Alpha Particles; D000818:Animals; D018480:Astronauts; D024201:Bystander Effect / Q000502:physiology*; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000473:pathology; D006224:Cricetinae; D003593:Cytoplasm / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D020450:Heavy Ions; D006801:Humans; D051379:Mice; D009154:Mutation; D009381:Neoplasms, Radiation-Induced / Q000209:etiology / Q000235:genetics / Q000473:pathology*; D010315:Particle Accelerators; D012306:Risk; D013026:Space Flight