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Lung cancer risk in human and rats:single vs.multiple cellular hits


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National Radiation Environment (NRE - VII), 20-24 May, 2002, Rhodes, Grèce

H. Fakir (1), W. Hofmann (2), I. Aubineau-Lanièce (3), R.S. Caswell (4), J.R. Jourdain (3) and A. Sabir (1)

Type de document > *Congrès/colloque

Mots clés > dosimétrie interne

Unité de recherche > Laboratoire d'évaluation et de modélisation de la dose interne (LEMDI)

Auteurs > JOURDAIN Jean-René

Date de publication > 22/11/2002

Résumé

At the cellular level, the use of an average dose is equivalent to the assumption that all cells receive the same dose, even at the lowest possible exposure, i.e., due to the emission of one alpha particle. In reality, however, only a small number of cells will be hit at low level exposures, while a relatively large amount of energy will be imparted to those cell nuclei which are actually hit by an alpha particle. There is growing evidence that the number of multiple cellular hits involved may play a crucial role in the extrapolation of lung cancer risk from high to low radon exposures. The quantitative assessment of multiple hits and the impact of this on dose assessments is therefore a crucial factor of the reliability of radon lung dosimetry. Indeed, even at relatively low exposure levels, the inhomogeneity of the deposition patterns for inhaled radon progeny within bronchial airway bifurcations, particularly at carinal ridges, may lead to localized radon progeny accumulations which can produce multiple hits in bronchial epithelial cells.
Based on a normalized surface activity of 1 Bq cm-2, the probability of hitting cell nuclei located at different depths in bronchial epithelium was obtained by a numerical integration over all surface elements lying within the maximum track lengths of emitted alpha particles. In the present study, cellular hit frequencies and fractions of cells hit by 218Po and 214Po alpha particles were computed for selected bronchial airway generations in human and rat lungs. In each airway generation, hit frequencies decreased in an almost linear fashion with increasing depth into epithelial tissue. Weighted by the depth-density distributions of basal and secretory in a giver airway generation, the individual hit frequencies, calculated for different depths in bronchial epithelium and different airway generations, were then reduced to an average hit frequency for the whole bronchial region. To relate these results to realistic inhalation conditions, steady-state 218Po and 214Po surface activities were computed for defined exposure conditions. These surface activities were normalized to a cumulative exposure of 1 working level month (WLM) to facilitate comparison with epidemiological data on lung cancer incidence.

The mathematical framework provided by microdosimetry can be used to illustrate the effect of single and multiple hits on cellular dose distributions [1]. Based on the surface activity patterns of radon progeny and the distributions of target cells, dose-dependent distributions of specific energy in sensitive cells, f(z;D), were calculated for the traversal of 0, 1, 2, or more alpha particles. Using Monte Carlo and analytical methods, f(z;D) can be obtained either directly from the simulation of the random trajectories of alpha particles, or in two successive steps : (i) firstly, cach event is taken individually, i.e., considering only the occurrence of exactly 1 event in the cell, f1(z) ; (ii) which is followed by successive convolutions of f1(z) in order to obtain f(z;D), describing both single and multiple cellular events. In the present study, f(z;D) distributions were computed for varying depths in bronchial epithelium for a few selected bronchial airway generations in human and rat lungs.

....... (the abstract had to be shortened)

This research was supported in part by CEC contracts no. FIGH-CT1999-00005 and no. FIGD-CT-2000-00053, and by the French-Austrian Amadee program, project no.III.1.
[1] Aubineau-Lanièce, I., Castellan, G., Caswell, R., Guezingar, F., Henge-Napoli, M.H., Li, W.B. and Pihet, P., Radiat. Prot. Dosim. 79, 395-400 (1998).
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(1) Laboratory of Nuclear Physics and Applications, Ibn Tofail University, Kenitra Morocco
(2) Institute of Physics and Biophysics, University of Salzburg, Hellbrunner Str. 34, A-5020 Salzburg, Austria
(3) Département de Protection de la Santé de l’Homme et de Dosimétrie, Institut de Radioprotection et de Sûreté Nucléaire (IRSN), B.P. 17, 92262 Fontenay-aux-Roses cedex, France
(4) National Institute of Standards and Technology, Gaithersburg, MD 20899, USA