title: A new perspective of carcinogenesis from protracted high-LET radiation arises from the two-stage clonal expansion model.
abstract: When applied to the Colorado Plateau miner population, the two-stage clonal expansion (TSCE) model of radiation carcinogenesis predicts that radiation-induced promotion dominates radiation-induced initiation. Thus, according to the model, at least for alpha-particle radiation from inhaled radon daughters, lung cancer induction over long periods of protracted irradiation appears to be dominated by radiation-induced modification of the proliferation kinetics of already-initiated cells rather than by direct radiation-induced initiation (i.e., mutation) of normal cells. We explore the possible consequences of this result for radiation exposures to space travelers on long missions. Still unknown is the LET dependence of this effect. Speculations of the cause of this phenomenon include the suggestion that modification of cell kinetics is caused by a "bystander" effect, i.e., the traversal of normal cells by alpha particles, followed by the signaling of these cells to nearby initiated cells which then modify their proliferation kinetics.
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, WA 98109-1024, USA.
authors.forename: S B
authors.initials: SB
authors.lastname: Curtis
authors.forename: E G
authors.initials: EG
authors.lastname: Luebeck
authors.forename: W D
authors.initials: WD
authors.lastname: Hazelton
authors.forename: S H
authors.initials: SH
authors.lastname: Moolgavkar
mesh_terms: D000512:Alpha Particles / Q000009:adverse effects*; D024201:Bystander Effect / Q000502:physiology; D003120:Colorado; D003359:Cosmic Radiation; D006801:Humans; D018499:Linear Energy Transfer; D008175:Lung Neoplasms / Q000453:epidemiology / Q000209:etiology; D008906:Mining; D008954:Models, Biological; D009381:Neoplasms, Radiation-Induced / Q000453:epidemiology / Q000209:etiology*; D016273:Occupational Exposure; D011829:Radiation Dosage; D011886:Radon; D018570:Risk Assessment; D013026:Space Flight; D013234:Stem Cells / Q000528:radiation effects
chemical_list: D011886:Radon