title: Mutation induction by inhaled radon progeny modeled at the tissue level.
abstract: The observable responses of living systems to ionizing radiation depend on the level of biological organization studied. Understanding the relationships between the responses characteristic of the different levels of organization is of crucial importance. The main objective of the present study is to investigate how some cellular effects of radiation manifest at the tissue level by modeling mutation induction due to chronic exposure to inhaled radon progeny. For this purpose, a mathematical model of the bronchial epithelium was elaborated to quantify cell nucleus hits and cell doses. Mutagenesis was modeled considering endogenous as well as radiation-induced DNA damages and cell cycle shortening due to cell inactivation. The model parameters describing the cellular effects of radiation are obtained from experimental data. Cell nucleus hits, cell doses, and mutation induction were computed for the activity hot spots of the large bronchi at different exposures. Results demonstrate that the mutagenic effect of densely ionizing radiation is dominated by cell cycle shortening due to cell inactivation and not by DNA damages. This suggests that radiation burdens of non-progenitor cells play a significant role in mutagenesis in case of protracted exposures to densely ionizing radiation. Mutation rate as a function of dose rate exhibits a convex shape below a threshold. This threshold indicates the exhaustion of the tissue regeneration capacity of local progenitor cells. It is suggested that progenitor cell hyperplasia occurs beyond the threshold dose rate, giving a possible explanation of the inverse dose-rate effect observed in the epidemiology of lung cancer among uranium miners.
authors: Hungarian Academy of Sciences KFKI Atomic Energy Research Institute, Budapest, Hungary. mabage@aeki.kfki.hu
authors: Balázs G
authors: BG
authors: Madas
authors: Imre
authors: I
authors: Balásházy
mesh_terms: D000512:Alpha Particles / Q000009:adverse effects; D000818:Animals; D001980:Bronchi / Q000166:cytology; D002450:Cell Communication / Q000528:radiation effects; D059447:Cell Cycle Checkpoints / Q000528:radiation effects; D002467:Cell Nucleus / Q000528:radiation effects; D002470:Cell Survival / Q000528:radiation effects; D004249:DNA Damage; D004307:Dose-Response Relationship, Radiation; D004848:Epithelium / Q000473:pathology / Q000528:radiation effects; D006801:Humans; D006965:Hyperplasia / Q000209:etiology; D001239:Inhalation; D008954:Models, Biological; D009154:Mutation; D011886:Radon / Q000009:adverse effects* / Q000737:chemistry*
chemical_list: D011886:Radon