Publications (263) View all
-
Article: A laboratory inter-comparison of the importance of serum serotonin levels in the measurement of a range of radiation-induced bystander effects: Overview of study and results presentation.
[show abstract] [hide abstract]
ABSTRACT: Abstract Purpose: Recent research has suggested that serotonin may play an important role in the expression of radiation-induced bystander effects. Serotonin levels in serum were reported to range from 6-22 μM and to correlate inversely with the magnitude of cellular colony-forming ability in medium transfer bystander assays. That is, high serotonin concentration correlated with a low cloning efficiency in cultures receiving medium derived from irradiated cells. Methods: Because of the potential importance of this observation, the European Union's Non-targeted Effects Integrated Project (NOTE) performed an inter-comparison exercise where serum samples with high and low serotonin levels were distributed to seven laboratories which then performed their own assay to determine the magnitude of the bystander effect. Results: The results provided some support for a role for serotonin in four of the laboratories. Two saw no difference between the samples and one gave inconclusive results. In this summary paper, full data sets are presented from laboratories whose data was inconclusive or insufficient for a full paper. Other data are published in full in the special issue. Conclusion: The data suggest that there may be multiple bystander effects and that the underlying mechanisms may be modulated by both the culture conditions and the intrinsic properties of the cells used in the assay.International Journal of Radiation Biology 08/2012; 88(10):763-9. · 2.28 Impact Factor -
Chapter: Genetic Effects of Bystander Factors from Serums of Affected by the Chernobyl Accident Populations
01/2012: pages 165-172; , ISBN: 978-1-61324-516-3 -
Article: Induction of bystander response in human glioma cells using high-energy electrons: a role for TGF-beta1.
[show abstract] [hide abstract]
ABSTRACT: We examined bystander cell death produced in T98G cells by exposure to irradiated cell conditioned medium (ICCM) produced by high-energy 20 MeV electrons at a dose rate of 10 Gy min(-1) and doses up to 20 Gy. ICCM induced a bystander response in T98G glioma cells, reducing recipient cell survival by more than 25% below controls at 5 and 10 Gy. Higher doses increased survival to near control levels. ICCM was analyzed for the presence of transforming growth factor alpha (TGF-alpha) and transforming growth factor beta1 (TGF-beta1). Monoclonal antibodies for TGF-alpha (mAb TGF-alpha) and TGF-beta1 (mAb TGF-beta1) were added to the ICCM to neutralize any potential effect of the cytokines. The results indicate that TGF-alpha was not present in the ICCM and addition of mAb TGF-alpha to the ICCM had no effect on bystander cell survival. No active TGF-beta1 was present in the ICCM; however, addition of mAb TGF-beta1 completely abolished bystander death of reporter cells at all doses. These results indicate that bystander cell death can be induced in T98G glioma if a large enough radiation stress is applied and that TGF-beta1 plays a downstream role in this response.Radiation Research 06/2010; 173(6):769-78. · 2.68 Impact Factor -
Article: Expression of delayed toxicity and lethal mutations in the progeny of human cells surviving exposure to radiation and other environmental mutagens
[show abstract] [hide abstract]
ABSTRACT: Purpose: Delayed expression of lethal mutations in the progeny of cells which survived a toxic insult was first shown for ionizing radiation and is one of the signs of induced genomic instability. The effect appears to be related to DNA strand breakage or repair but not to the physical break itself. To investigate this and the relationship of lethal mutations or delayed death to other instability endpoints, cultures of immortal but non-transformed human keratinocytes were exposed to a range of environmental mutagens or cytotoxic compounds with different DNA damaging properties. Methods: Delayed expression of damage was assessed by scoring a number of endpoints in the progeny of cells which survived exposure and underwent at least 15 population doublings. Endpoints included delayed apoptosis, cloning efficiency of cells in 'healthy' colonies and expression of the apoptosis regulatory proteins bcl-2 and BAX. Results: The results clearly linked expression of delayed lethal mutations with substances that induced DNA strand breaks. All these substances are known also to induce oxidative stress. The occurrence of delayed damage required a threshold level of toxicity in the initially exposed population, which was remarkably similar for all the e ffective substances except cadmium. Alkylating agents or microtubule poisons that do not permit repair of DNA damage did not cause any delayed death. Conclusion: It is concluded that delayed cell death may be caused by widespread radical damage to DNA which is either signalled, thereby inducing an apoptotic response, or (mis-)repaired yielding a weak or unstable genome. It is likely that the process may be an important factor in determining the long-term response of populations to 'sublethal' levels of environmental mutagens whose mechanism of action includes DNA strand breakage and repair.07/2009; 74(6):673-680. -
Article: Bystander effect induced changes in apoptosis related proteins and terminal differentiation in in vitro murine bladder cultures.
[show abstract] [hide abstract]
ABSTRACT: Radiation-induced bystander effects are now an established phenomenon seen in numerous cell and tissue culture models. The aim of this investigation was to examine the bystander signal and response in a multicellular primary tissue culture system in vitro. Murine bladder samples were explanted and directly exposed to gamma radiation, or treated with irradiated tissue conditioned medium (ITCM) generated from the directly irradiated cultures. Results indicated that there was a strong bystander signal produced by the tissue that caused both dose-dependent and -independent changes in the ITCM treated tissue. Significantly increased B-cell lymphoma 2 (Bcl2) expression was noted after treatment with 0.5Gy and 5Gy ITCM (approximately 80%), while dose-dependent changes were observed in c-myelocytomatosis (cMyc) (39.48% at 0.5 Gy ITCM, 81.28% at 5 Gy ITCM) and the terminal differentiation marker uroplakin III (17.88% at 0.5 Gy). Nuclear fragmentation was also significantly increased at both doses of ITCM. These data suggest that the bystander signal produced in a multicellular environment induces complex changes in the ITCM-treated culture, and that these changes are reflective of a coordinated response to maintain integrity throughout the tissue.International Journal of Radiation Biology 02/2009; 85(1):48-56. · 2.28 Impact Factor
