Journal Article

The time and spatial effects of bystander response in mammalian cells induced by low dose radiation

Burong Hu, Lijun Wu, Wei Han, Leilei Zhang, Shaopeng Chen, An Xu, Tom K. Hei and Zengliang Yu

in Carcinogenesis

Volume 27, issue 2, pages 245-251
Published in print February 2006 | ISSN: 0143-3334
Published online September 2005 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgi224
The time and spatial effects of bystander response in mammalian cells induced by low dose radiation

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Bystander effects induced by low dose of ionizing radiation have been shown to widely exist in many cell types and may have a significant impact on radiation risk assessment. Though many studies have been reported on this phenomenological observation, the mechanisms underlying this process are not clear, especially on the questions of how soon after irradiation the bystander effects can be initiated and how far this bystander signal can be propagated once it is started. DNA double-strand breaks (DSBs) induced by ionizing radiation or carcinogenic chemicals can be visualized in situ using γ-H2AX immunofluorescent staining. Our previous studies have shown that in situ visualization of DSBs could be used to assess irradiation-induced extranuclear/extracellular (bystander) effect at an early stage after irradiation. In the present studies, we used this method to investigate the time and spatial effects of damage signals on unirradiated bystander cells. The results showed that increased DSBs in irradiated and unirradiated bystander areas could be visualized 2 min after radiation and reached its maximum 30 min after radiation. The average levels of DSB formation at 30 min post-1cGy irradiation in the irradiated and unirradiated bystander areas were 3-fold and 2-fold higher than those of the sham-irradiated control cells, respectively. Afterwards, the formation of DSBs declined with incubation time and remained steady for at least 6 h at a level that was statistically higher than their controls. The results also showed that the bystander signal derived from irradiated cells could be transferred to anywhere in the dish and the percentage of DSBs in the unirradiated bystander cells was not dependent on the dose delivered. Moreover, the fraction of DSB positive cells in unirradiated bystander areas showed a time-dependent increase based on its distance to the irradiated area at very early stage post-irradiation. Both lindane and DMSO significantly suppressed the yield of DSBs in the cells of unirradiated bystander areas, which suggest that gap junctional intercellular communication and reactive oxygen species played important roles in the induction of the bystander effects, both in irradiated and unirradiated bystander areas.

Keywords: DSBs, double-strand breaks; GJIC, gap junctional intercellular communication; MN, micronucleus; RIBE, radiation-induced bystander effects; ROS, reactive oxygen species; SCE, sister chromatid exchange; PCNA, proliferating cell nuclear antigen

Journal Article.  5284 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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