Lorna A Ryan

McMaster University, Hamilton, Ontario, Canada

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Publications (5)10.85 Total impact

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    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. · 2.70 Impact Factor
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    ABSTRACT: A previous study comparing the bystander effect and low-dose hypersensitivity found that they were inversely correlated. In the current study seven cell lines with established bystander effect and hyper-radiosensitivity/increased radioresistance (HRS/IRR) were further screened for the presence of an adaptive response. Cell survival after exposure to direct radiation with or without a 0.1 Gy priming dose, was determined using the colony forming assay for seven human cell lines (HaCAT, HPV-G, SW48, T98G, U373, HGL21 and HT29). Furthermore, the impact of the bystander effect on cell survival after exposure to irradiated cell culture medium was measured concurrently. An adaptive response was induced in four cell lines (U373, T98G, HGL21 and HT29) causing increased cell survival. In agreement with previous publications, a bystander effect was induced in three cell lines (HPV-G, HaCAT and SW48); while no bystander effect was seen in U373, T98G, HGL21 and HT29. An adaptive response was detected in cell lines known to produce hypersensitive response, and was inversely correlated with the bystander effect. These results suggest that for the cell lines tested the ability to induce an adaptive response may be mutually exclusive to the bystander effect.
    International Journal of Radiation Biology 02/2009; 85(1):87-95. · 1.84 Impact Factor
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    ABSTRACT: Two almost completely exclusive fields in radiobiology deal with splitting doses of radiation and comparing the effect to a similar total dose given in one exposure. In radiotherapy, dose "fractionation" is used to "spare" normal tissue and in the low dose field, the adaptive response is well documented as a phenomenon where a small "priming" dose administered before the larger "challenge" dose reduces the effect of the large dose. There have been very few studies where these fields overlap, thus it is not possible to ascertain whether common or distinct mechanisms underlie both phenomena but this is certainly an interesting question and relevant to our understanding of high and low dose radiobiology. This paper presents data for three human cell lines with varying p53 status and radiation responses, treated at a range of times between first and second dose and for 3 different first doses (0.1, 0.5 and 2Gy). The data show that time between doses is critical. Protective (adaptive) effects were seen in each cell line but most prominently in the malignant HT 29 cell line. Surprisingly none of the cell lines showed pronounced split dose recovery. This suggests different mechanisms may underlie the two phenomena.
    Dose-Response 01/2009; 7(4):292-306. · 1.50 Impact Factor
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    ABSTRACT: There is considerable interest at present in low-dose radiation effects in non-human species. In this study gamma radiation-induced adaptive response, a low-dose radiation effect, was examined in three fish cell lines, (CHSE-214 (Chinook salmon), RTG-2 (rainbow trout) and ZEB-2J (zebrafish)). Cell survival after exposure to direct radiation with or without a 0.1 Gy priming dose, was determined using the colony forming assay for each cell line. Additionally, the occurrence of a bystander effect was examined by measuring the effect of irradiated cell culture medium from the fish cell lines on unexposed reporter cells. A non-linear dose response was observed for all cell lines. ZEB-2J cells were very sensitive to low doses and a hyper-radiosensitive (HRS) response was observed for doses <0.5 Gy. A typical protective adaptive response was not detected in any of the three fish cell lines tested. Rather, it was found that pre-exposure of these cells to 0.1 Gy radiation sensitized the cells to subsequent high doses. In CHSE-214 cells, increased sensitivity to subsequent high doses of radiation was observed when the priming and challenge doses were separated by 4 h; however, this sensitizing effect was no longer present when the interval between doses was greater than 8 h. Additionally, a "protective" bystander response was observed in these cell lines; exposure to irradiated medium from fish cells caused increased cloning efficiency in unirradiated reporter cells. The data confirm previous conclusions for mammalian cells that the adaptive response and bystander effect are inversely correlated and contrary to expectations probably have different underlying mechanisms.
    Journal of Environmental Radioactivity 04/2008; 99(4):739-47. · 2.12 Impact Factor
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    ABSTRACT: While nontargeted and low-dose effects such as the bystander effect are now accepted, the mechanisms underlying the response have yet to be elucidated. It has been shown that the transfer of irradiated cell conditioned medium (ICCM) can kill cells that are not directly irradiated; however, to date the effect of ICCM concentration on cell killing has not been reported. The occurrence of a bystander effect was determined by measuring cell survival after exposure to various ICCM dilutions, using the colony-forming assay, in cells of six human cell lines with varied bystander responses and tumor/ p53 status. Autologous ICCM transfer for these cell lines induced a bystander effect as reported previously. ICCM from these cell lines was transferred to cells of a common reporter cell line (HPV-G) to investigate whether the lack of an induced bystander effect was due to their inability to generate or to respond to a bystander signal(s). ICCM from cells of four cell lines induced a bystander effect in HPV-G reporter cells, confirming that signal production is a critical factor. A saturation response was observed when ICCM was diluted. Survival was found to increase linearly until a plateau was reached and the bystander effect was abolished at 2x dilution. The effect of ICCM from the different cell lines reached a plateau at different dilutions, which were found to correlate with the cell line's radiosensitivity.
    Radiation Research 03/2008; 169(2):188-96. · 2.70 Impact Factor