Biology Based Lung Cancer Model for Chronic Low Radon Exposures
- Conference date: 07–12 October 2007
- Location: Buzios, Rio de Janeiro (Brazil)
Low dose effects of alpha particles at the tissue level are characterized by the interaction of single alpha particles, affecting only a small fraction of the cells within that tissue. Alpha particle intersections of bronchial target cells during a given exposure period were simulated by an initiation‐promotion model, formulated in terms of cellular hits within the cycle time of the cell (dose‐rate) and then integrated over the whole exposure period (dose). For a given average number of cellular hits during the lifetime of bronchial cells, the actual number of single and multiple hits was selected from a Poisson distribution. While oncogenic transformation is interpreted as the primary initiation step, stimulated mitosis by killing adjacent cells is assumed to be the primary radiological promotion event. Analytical initiation and promotion functions were derived from experimental in vitro data on oncogenic transformation and cellular survival.
To investigate the shape of the lung cancer risk function at chronic, low level exposures in more detail, additional biological factors describing the tissue response and operating specifically at low doses were incorporated into the initiation‐promotion model. These mechanisms modifying the initial response at the cellular level were: adaptive response, genomic instability, induction of apoptosis by surrounding cells, and detrimental as well as protective bystander mechanisms. To quantify the effects of these mechanisms as functions of dose, analytical functions were derived from the experimental evidence presently available. Predictions of lung cancer risk, including these mechanisms, exhibit a distinct sublinear dose‐response relationship at low exposures, particularly for very low exposure rates.
- Alpha particles
- Biomedical modeling
- Cell division
- Probability theory
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Y. K. Semertzidis, M. Aoki, M. Auzinsh, V. Balakin, A. Bazhan, G. W. Bennett, R. M. Carey, P. Cushman, P. T. Debevec, A. Dudnikov, F. J. M. Farley, D. W. Hertzog, M. Iwasaki, K. Jungmann, D. Kawall, B. Khazin, I. B. Khriplovich, B. Kirk, Y. Kuno, D. M. Lazarus, L. B. Leipuner, V. Logashenko, K. R. Lynch, W. J. Marciano, R. McNabb, W. Meng, J. P. Miller, W. M. Morse, C. J. G. Onderwater, Y. F. Orlov, C. S. Ozben, R. Prigl, S. Rescia, B. L. Roberts, N. Shafer‐Ray, A. Silenko, E. J. Stephenson, K. Yoshimura and EDM Collaboration
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