Environmental Health Perspectives 105, Supplement 5, September 1997

[ Citation in PubMed ] [ Related Articles ]

A New Mechanism for DNA Alterations Induced by Alpha Particles Such as Those Emitted by Radon and Radon Progeny

Bruce E. Lehnert and Edwin H. Goodwin

Cell and Molecular Biology Group, Life Sciences Division, Los Alamos National Laboratory, Los Alamos, New Mexico

Abstract
The mechanism(s) by which alpha ( alpha ) particles like those emitted from inhaled radon and radon progeny cause their carcinogenic effects in the lung remains unclear. Although direct nuclear traversals by alpha -particles may be involved in mediating these outcomes, increasing evidence indicates that a particles can cause alterations in DNA in the absence of direct hits to cell nuclei. Using the occurrence of excessive sister chromatid exchanges (SCE) as an index of DNA damage in human lung fibroblasts, we investigated the hypothesis that alpha -particles may induce DNA damage through the generation of extracellular factors. We have found that a relatively low dose of alpha -particles can result in the generation of extracellular factors, which, upon transfer to unexposed normal human cells, can cause excessive SCE to an extent equivalent to that observed when the cells are directly irradiated with the same irradiation dose. A short-lived, SCE-inducing factor(s) is generated in alpha -irradiated culture medium containing serum in the absence of cells. A more persistent SCE-inducing factor(s), which can survive freeze-thaw and is heat labile is produced by fibroblasts after exposure to the alpha -particles. These results indicate that the initiating target for alpha -particle-induced genetic changes can be larger than a cell's nucleus or even a whole cell. How transmissible factors like those observed here in vitro may extend to the in vivo condition in the context of a-particle-induced carcinogenesis in the respiratory tract remains to be determined. -- Environ Health Perspect 105(Suppl 5):1095-1101 (1997)

Key words : alpha particles, radon/radon progeny, indirect radiation effects, high LET radiation, DNA damage, extracellular factors, sister chromatid exchange, human lung fibroblasts

This paper is based on a presentation at The Sixth International Meeting on the Toxicology of Natural and Man-Made Fibrous and Non-Fibrous Particles held 15-18 September 1996 in Lake Placid, New York. Manuscript received at EHP 26 March 1997; accepted 15 July 1997.
This investigation was supported by U.S. Department of Energy-funded projects titled "Latent Expression of Genetic Damage in Human Lung Cells Caused by alpha -Particles and alpha -Rays," "Mechanisms of Pulmonary Damage," and "Chromosome Damage in the One Rad Region"; the work was conducted under the auspices of the Department of Energy. The authors thank A. Deshpande, S.M. Bailey, and R.T. Svensson for their technical assistance during the course of this study.
Address correspondence to Dr. B.E. Lehnert, Cell and Molecular Biology Group, LS-4, Life Sciences Division, MS M888, Los Alamos National Laboratory, Los Alamos, New Mexico 87545. Telephone: (505) 667-2753. Fax: (505) 665-3024. E-mail: lehnert@telomere.lanl.gov
Abbreviations used: alpha -particles, alpha particles; cGy, centigray; FBS, fetal bovine serum; HFL1, human lung fibroblasts; LET, linear energy transfer; MEM, minimum essential medium; SCE, sister chromatid exchange(s).

[ Table of Contents ] [ Full Article ] [ Citation in PubMed ] [ Related Articles ]

Last Update: October 27, 1997