title: Application of Bayesian inference to characterize risks associated with low doses of low-LET radiation.
abstract: Improved risk characterization for stochastic biological effects of low doses of low-LET radiation is important for protecting nuclear workers and the public from harm from radiation exposure. Here we present a Bayesian approach to characterize risks of stochastic effects from low doses of low-LET radiation. The stochastic effect considered is neoplastic transformation of cells because it relates closely to cancer induction. We have used a published model of neoplastic transformation called NEOTRANS1. It is based on two different classes of cellular sensitivity for asynchronous, exponentially growing populations (in vitro). One sensitivity class is the hypersensitive cell; the other is the resistant cell. NEOTRANS1 includes the effects of genomic damage accumulation, DNA repair during cell cycle arrest, and DNA misrepair (non-lethal repair errors). The model-associated differential equations are solved for conditions of in vitro irradiation at a fixed rate. Previously published solutions apply only to high dose rates and were incorrectly assumed to apply to only high-LET radiation. Solutions provided here apply to any fixed dose rate and to both high- and low-LET radiations. Markov chain Monte Carlo methods are used to carry out the Bayesian inference of the low-dose risk for neoplastic transformation of aneuploid C3H 10T1/2 cells for X-ray doses from 0 to 1000 mGy. We have assumed that for this low-dose range only the hypersensitive fraction of the cells are affected. Our results indicate that the initial slope of the risk vs dose relationship for neoplastic transformation is as follows: (1) directly proportional to the fraction, f1, of hypersensitive cells; (2) directly proportional to the radiosensitivity of the genomic target; and (3) inversely proportional to the rate at which hypersensitive cells with radiation-induced damage are committed to undergo correct repair of genomic damage. Further, our results indicate that very fast molecular events are associated with the commitment of cells to the correct repair pathway. Results also indicate a relatively large probability for misrepair that leads to genomic instability. Our results are consistent with the view that for very low doses, dose rate is not an important variable for characterizing low-LET radiation risks so long as age-related changes in sensitivity do not occur during irradiation.
authors.affiliation: Lovelace Respiratory Research Institute, Inhalation Toxicology Laboratory, P.O. Box 5890, Albuquerque, New Mexico 87185-5890, USA. schoellnberger@sbg.ac.at, bscott@lrri.org
authors.forename: H
authors.initials: H
authors.lastname: Schöllnberger
authors.forename: B R
authors.initials: BR
authors.lastname: Scott
authors.forename: T E
authors.initials: TE
authors.lastname: Hanson
mesh_terms: D000818:Animals; D001499:Bayes Theorem; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000528:radiation effects*; D002478:Cells, Cultured; D003198:Computer Simulation; D004249:DNA Damage / Q000502:physiology; D004260:DNA Repair / Q000502:physiology; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D018499:Linear Energy Transfer; D051379:Mice; D008809:Mice, Inbred C3H; D008954:Models, Biological; D009010:Monte Carlo Method