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Induction of a bystander mutagenic effect of alpha particles in mammalian cellsEver since the discovery of X-rays was made by Rontgen more than a hundred years ago, it has always been accepted that the deleterious effects of ionizing radiation such as mutation and carcinogenesis are attributable mainly to direct damage to DNA. Although evidence based on microdosimetric estimation in support of a bystander effect appears to be consistent, direct proof of such extranuclear/extracellular effects are limited. Using a precision charged particle microbeam, we show here that irradiation of 20% of randomly selected A(L) cells with 20 alpha particles each results in a mutant fraction that is 3-fold higher than expected, assuming no bystander modulation effect. Furthermore, analysis by multiplex PCR shows that the types of mutants induced are significantly different from those of spontaneous origin. Pretreatment of cells with the radical scavenger DMSO had no effect on the mutagenic incidence. In contrast, cells pretreated with a 40 microM dose of lindane, which inhibits cell-cell communication, significantly decreased the mutant yield. The doses of DMSO and lindane used in these experiments are nontoxic and nonmutagenic. We further examined the mutagenic yield when 5-10% of randomly selected cells were irradiated with 20 alpha particles each. Results showed, likewise, a higher mutant yield than expected assuming no bystander effects. Our studies provide clear evidence that irradiated cells can induce a bystander mutagenic response in neighboring cells not directly traversed by alpha particles and that cell-cell communication process play a critical role in mediating the bystander phenomenon.
Document ID
20040141663
Acquisition Source
Legacy CDMS
Document Type
Reprint (Version printed in journal)
External Source(s)
Authors
Zhou, H.
(College of Physicians and Surgeons, School of Public Health, Columbia University and Environmental Health Sciences, New York, NY 10032, United States)
Randers-Pehrson, G.
Waldren, C. A.
Vannais, D.
Hall, E. J.
Hei, T. K.
Chatterjee, A.
Date Acquired
August 22, 2013
Publication Date
February 29, 2000
Publication Information
Publication: Proceedings of the National Academy of Sciences of the United States of America
Volume: 97
Issue: 5
ISSN: 0027-8424
Subject Category
Life Sciences (General)
Funding Number(s)
CONTRACT_GRANT: CA 49062
CONTRACT_GRANT: CA 36447
CONTRACT_GRANT: CA 75384
Distribution Limits
Public
Copyright
Other
Keywords
Non-NASA Center
NASA Discipline Radiation Health

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