title: Towards a unifying theory of late stochastic effects of ionizing radiation.
abstract: The traditionally accepted biological basis for the late stochastic effects of ionizing radiation (cancer and hereditary disease), i.e. target theory, has so far been unable to accommodate the more recent findings of non-cancer disease and the so-called non-targeted effects, genomic instability and bystander effect, thus creating uncertainty in radiation risk estimation. We propose that ionizing radiation can give rise to these effects through two distinct and independent routes, one essentially genetic, termed here type A, and the other essentially epigenetic, termed type B. Type B processes entail envisaging phenotype as represented by a dynamic attractor and radiation acting as an agent that stresses cellular processes leading to the adoption of a variant attractor/phenotype. Evidence from the literature indicates that type B processes can lead to the inheritance of variant cell attractors and mediate a category of trans-generational effects quite distinct from classical Mendelian inherited disease, which is type A. The causal relationships for radiation-induced somatic human health detriment, i.e., cancer and non-cancer (e.g., cardiovascular) disease, are discussed from the point of view of the proposed classification. This approach unifies at a fundamental level the heritable and late somatic effects of radiation into a single causal framework that has the potential to be extended to the effects of the other environmental agents damaging to health.
authors.affiliation: Department of Environmental Science, University of Eastern Finland, Kuopio Campus, PL 1627, 70211 Kuopio, Finland. keith.baverstock@uef.fi
authors.forename: Keith
authors.initials: K
authors.lastname: Baverstock
authors.forename: Andrei V
authors.initials: AV
authors.lastname: Karotki
mesh_terms: D000818:Animals; D024201:Bystander Effect / Q000528:radiation effects; D044127:Epigenesis, Genetic / Q000528:radiation effects; D030342:Genetic Diseases, Inborn / Q000209:etiology; D042822:Genomic Instability / Q000528:radiation effects; D005854:Germ Cells / Q000528:radiation effects; D006801:Humans; D008954:Models, Biological; D008957:Models, Genetic; D009154:Mutation; D009381:Neoplasms, Radiation-Induced / Q000235:genetics; D011830:Radiation Effects; D011831:Radiation Genetics; D018570:Risk Assessment; D013269:Stochastic Processes