title: The role of promotion in carcinogenesis from protracted high-LET exposure.
abstract: Recent analysis of epidemiological studies using the two-stage clonal expansion (TSCE) model has shown that radiation-induced promotion dominates radiation-induced initiation for protracted exposures to radon. This strong promotion effect (i.e. enhanced proliferation of already-initiated cells) causes a pronounced 'inverse dose-rate effect', but by a mechanism completely different from those usually discussed in this connection. This rather startling result is discussed along with implications to extended space missions that include a significant amount of high-LET radiation. It is suggested that the effect might be caused by a 'Bystander Effect' by which normal cells in the vicinity of initiated cells are hit by alpha particles and send out signals that modify the cell kinetics of the already-initiated clones.
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, WA 98109, 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: D000328:Adult; D000368:Aged; D000512:Alpha Particles; D024201:Bystander Effect; D002471:Cell Transformation, Neoplastic; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D018499:Linear Energy Transfer; D008175:Lung Neoplasms / Q000209:etiology* / Q000401:mortality; D008875:Middle Aged; D008906:Mining; D008954:Models, Biological; D009154:Mutation; D009381:Neoplasms, Radiation-Induced / Q000209:etiology* / Q000401:mortality; D011886:Radon; D012062:Relative Biological Effectiveness; D012306:Risk
chemical_list: D011886:Radon