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Genomic instability and bystander effects induced by high-LET radiation

Oncogene volume 22, pages 7034–7042 (2003)Cite this article

Abstract

An understanding of the radiobiological effects of high-linear energy transfer (LET) radiation is essential for radiation protection and human risk assessment. Ever since the discovery of X-rays was made by Röntgen more than a century ago, it has always been accepted that the deleterious effects of ionizing radiation, such as mutation and carcinogenesis, are due mainly to direct damage to DNA. With the availability of a precision single-particle microbeam, it is possible to demonstrate, unequivocally, the presence of a bystander effect with many biological end points. These studies provide clear evidence that irradiated cells can induce a bystander mutagenic response in neighboring cells not directly traversed by α-particles, and that cell–cell communication processes play a critical role in mediating the bystander phenomenon. Following exposure to high-LET radiation, immortalized human bronchial (BEP2D) and breast (MCF-10F) cells have been shown to undergo malignant transformation through a series of successive steps, before becoming tumorigenic in nude mice. There is a progressive increase in genomic instability, determined either by gene amplification or allelic imbalance, with the highest incidence observed among established tumor cell lines, relative to transformed, nontumorigenic and control cell lines.

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Acknowledgements

We thank Dr Catherine Mitchell for critical reading of the manuscript. This work was supported by funding from the National Institute of Health grants CA 49062, ES 07890, NIH Resource Center Grant RR 11623, Environmental Center grant ES 10349 and from the US Department of Energy DEFG-ER63441.

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  1. Center for Radiological Research, and The Herbert Irving Comprehensive Cancer Center, College of Physicians & Surgeons, Columbia University, 630 West 168th Street, New York, 10032, NY, USA

    Eric J Hall & Tom K Hei

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Correspondence to Eric J Hall.

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Hall, E., Hei, T. Genomic instability and bystander effects induced by high-LET radiation. Oncogene 22, 7034–7042 (2003). https://doi.org/10.1038/sj.onc.1206900

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