The Biological Effectiveness of Radon-Progeny Alpha Particles. II. Oncogenic Transformation as a Function of Linear Energy Transfer

Abstract

Epidemiological studies have established an association between exposure to radon and carcinoma of the lung. However, based on data for either lung cancer in uranium miners exposed to radon or bronchial epithelial carcinomas in Japanese A-bomb survivors, it has not been possible to assign estimates of risk of lung cancer for the general population exposed to radon in their homes. Based on past success with the excellent quantitative properties of the C3H 10T1/2 in vitro oncogenic transformation assay system, the relative biological effectiveness (RBE) for radiation-induced transformation for charged particles of defined LET has been determined. As the LET of the radiation was increased, the rate of induction of oncogenic transformation increased and the RBEm approached 20. At higher LETs, RBE dropped precipitously. The rapid drop in effectiveness for alpha particles with LETs between 120 and 265 keV/microns implies a lower quality factor than the 20-25 currently considered appropriate when estimating lung cancer mortality.

Human Lung Cancer Risks from Radon – Part III - Evidence of Influence of Combined Bystander and Adaptive Response Effects on Radon Case-Control Studies - A Microdose Analysis

“…Based on the extensive studies of in vitro alpha particle cellular dose response to ionizing radiations (Miller et al 1995, 1999, Zhou et al 2001, 2004, Nagasawa and Little 1999, 2002, Nagasawa et al 2003, Hei et al 1997, Sawant et al 2001 and analyzed in Part I, there has been a presumption that the Bystander Effect is experienced by humans in the induction of radon induced lung cancer (Zhou et al 2001, Brenner and Sachs 2002, Little and Wakeford 2001, Little 2004). The extensive Adaptive Response in vitro research cited here (Azzam et al 1996, Elmore et al 2006, Ko et al 2004, Redpath et al 2001, Redpath and Antoniono 1998, Shadley and Wiencke 1989, Wiencke et al 1986, Wolff et al 1989 and analyzed with the composite AR and BE Microdose Model (Leonard 2005, 2008a, 2008b) is supportive of humans experiencing Adaptive Response radio-protection from low LET radiation exposures.…”

“…Neither alpha particle bystander nor low LET adaptive response or combined in vitro experiments have been conducted, to a reasonable extent, directly with the basal and secretory lung cells. The alpha particle LET and RBE broadbeam in vitro experiments of Miller et al (1995) need to be repeated with immortalized basal and secretory cells. Similarly, the low LET adaptive response experiments of Dr. Redpaths group need to be repeated with the immortalized basal and secretory cells.…”

Human Lung Cancer Risks from Radon – Part I - Influence from Bystander Effects - A Microdose Analysis

“…The modified BaD Model best fit to the Miller et al (1995) exposure of C3H 10T1/2 cells to alpha particles of indicated range of LETs. Experiments are described in Section 3.1.e and 4.1.c and best fit parameters are given in Table 1. Damage Region and the Direct Damage Region, along with the RBE values reported by Miller et al (1995) in their Figure 3. We show a significant difference between the Bystander and Direct Damage values and between these and the Miller et al (1995) values.…”

Radiotoxicity of Gadolinium-148 and Radium-223 in Mouse Testes: Relative Biological Effectiveness of Alpha-Particle Emitters In Vivo

“…Briefly, the mean testicular absorbed dose D is given by (26) (2) where the cumulated activity à is the time integral of the activity in the organ ∫A(t)dt, Δ is the mean energy emitted per nuclear transition, φ is the absorbed fraction, m is the average mass of the testis (0.1 g), and i denotes the ith radiation component emitted by the radionuclide. In keeping with our dosimetry procedures for an optimal assay day of 36 days after injection, the cumulated activity was integrated over 13 days (8,11).…”

“…For in vitro studies, the RBE is strongly dependent on LET with a maximum at about 120 keV/μm. Similarly, Miller et al (2) have investigated oncogenic transformation as a function of LET in cultured C3H 10T1/2 cells and found that the RBE for stochastic effects (RBE M ) is also maximum at about 120 keV/μm. Although there is a relative abundance of such data obtained in vitro, there are few studies investigating the relationship between RBE and LET in vivo.…”