title: Interrelationships between radiation-induced mutations and modifications in gene expression linked to cancer.
abstract: Ionizing radiation induces cancer in humans, but the mechanisms are not established. One simple way by which radiation could induce cancer is by inducing a genetic mutation in one or more of the multiple steps in the oncogenic pathway. However, many investigators favor the hypothesis that a mutator phenotype is necessary for a single cell to acquire the multiple genetic changes found in cancer. The alternative idea that ionizing radiation might induce an epigenetic heritable mutator phenotype has gained momentum in the last decade or so. A number of laboratories have observed a phenomenon termed 'delayed reproductive death', which is manifested as a reduced cloning efficiency, and also increased frequencies of gene locus mutations or chromosome aberrations that persist for many generations after radiation exposure. It is theorized that these endpoints arise due to a long-lived alteration in gene expression induced by radiation. Ionizing radiation is well known to induce gene expression, as it triggers the p53 pathway, as well as a series of early response genes, including c-jun and egr-I. However, there is no model from the gene expression field that could account for an epigenetic mutator effect that persists for tens or even hundreds of generations.
authors.affiliation: Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston 02114-2617, USA.
authors.forename: H L
authors.initials: HL
authors.lastname: Liber
authors.forename: E N
authors.initials: EN
authors.lastname: Phillips
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D002273:Carcinogens; D002471:Cell Transformation, Neoplastic; D015972:Gene Expression Regulation, Neoplastic / Q000528:radiation effects*; D006801:Humans; D009153:Mutagens; D009154:Mutation; D009381:Neoplasms, Radiation-Induced / Q000235:genetics*; D011839:Radiation, Ionizing
chemical_list: D002273:Carcinogens; D009153:Mutagens