Page 223 - 2014 Printable Abstract Book
P. 223
the underlying mechanisms are of relevance for radiation protection as well as for the clinical applications
of radiation in medicine. However, due to the variability in response depending on the model systems
used and radiation conditions, there is a need to further study under what conditions adaptive response
can be verified and the mechanisms involved. In this ongoing work, we study if there is a dose rate
dependence for the priming dose, assuming that the induction of DNA response/repair pathways are dose
rate dependent for the low doses usually applied. To address this issue we have chosen two cell types
(TK6 and MCF-10) and different dose rates for the same priming dose. Briefly, cells were exposed to a 50
mGy priming dose administered at high (0.4 Gy/min), or chronic (1.4 mGy/h or 4.1 mGy/h) dose rates.
After 4 hours incubation time cells were exposed to a challenging dose of 0.5 or 1 Gy. Adaptive response
was studied at the level of clonogenic survival and induction of HPRT mutation.
Based on our preliminary results, neither of the cell types showed an adaptive response at the level of
survival. The results from the mutation assay are ongoing and will be presented together with the survival
data.
(PS3-62) Measurement of inflammatory cytokines during Gastrointestinal Acute Radiation Syndrome
(GI-ARS). Aude-Marine Bonavita, MSc; Matthew Brown; Greg Tudor; and Cath Booth; Epistem Ltd,
Manchester, United Kingdom
Weight loss, diarrhea and an increased infection risk are common symptoms of GI-ARS. Following
total body X-irradiation, the integrity of the mucous membrane in the gut is rapidly compromised while
ulceration and inflammation of the tissue develop. Inflammatory cytokines, and more specifically the
balance between pro- and anti-inflammatory cytokines, are key for the regulation of the initiation,
progression and severity of the inflammation response. The magnetic-bead assay allows a rapid overview
of cytokine profiles specific to each tissue and is an easy method to test the efficacy of medical
countermeasures in a dose and time response manner. The assay was used on GI-ARS samples generated
by MCART studies to observe the effect of high dose X-irradiation on the level and time course of cytokines
present in plasma and different sections of the gastrointestinal tract. Tissue lysates were prepared at a
range of timepoints from 10-12 week old C57Bl/6 mice following 13Gy irradiation. The pro-inflammatory
cytokines IL-6, IL-1β and TNFα were measured alongside the anti-inflammatory IFNg, IL-13 and IL-10.
Within the tissues each cytokine profile was specific and varied with intestinal region, possibly reflecting
the differing kinetcs of ulceration in the small intestine and mid colon, and the flora present and
translocating post irradiation. For example, whilst levels of TNFα rise post irradiation, the response is more
dramatic and sustained in the mid colon compared to the small intestine. It was also clear that the soft
tissue responses differed from that of the plasma. The plasma is likely to integrate the response from
many organs and hence notoriously difficult to interpret and use as biomarker of GI damage. However,
temporal changes in local tissue cytokines may help identify intervention points and pathways for novel
therapies and radiation countermeasures. Furthermore, characterisation of the protein levels, rather than
the mRNA (as is often described) is more representative of the active inflammatory response. Ongoing
studies are investigating the longer term cytokine profiles changes associated with the delayed effects of
acute radiation exposure (DEARE) and links to organ-specific fibrosis. Funded in part by US Federal funds
from NIAID, NIH, and DHHS: Contract No: HHSN272201000046C.
221 | P a g e
of radiation in medicine. However, due to the variability in response depending on the model systems
used and radiation conditions, there is a need to further study under what conditions adaptive response
can be verified and the mechanisms involved. In this ongoing work, we study if there is a dose rate
dependence for the priming dose, assuming that the induction of DNA response/repair pathways are dose
rate dependent for the low doses usually applied. To address this issue we have chosen two cell types
(TK6 and MCF-10) and different dose rates for the same priming dose. Briefly, cells were exposed to a 50
mGy priming dose administered at high (0.4 Gy/min), or chronic (1.4 mGy/h or 4.1 mGy/h) dose rates.
After 4 hours incubation time cells were exposed to a challenging dose of 0.5 or 1 Gy. Adaptive response
was studied at the level of clonogenic survival and induction of HPRT mutation.
Based on our preliminary results, neither of the cell types showed an adaptive response at the level of
survival. The results from the mutation assay are ongoing and will be presented together with the survival
data.
(PS3-62) Measurement of inflammatory cytokines during Gastrointestinal Acute Radiation Syndrome
(GI-ARS). Aude-Marine Bonavita, MSc; Matthew Brown; Greg Tudor; and Cath Booth; Epistem Ltd,
Manchester, United Kingdom
Weight loss, diarrhea and an increased infection risk are common symptoms of GI-ARS. Following
total body X-irradiation, the integrity of the mucous membrane in the gut is rapidly compromised while
ulceration and inflammation of the tissue develop. Inflammatory cytokines, and more specifically the
balance between pro- and anti-inflammatory cytokines, are key for the regulation of the initiation,
progression and severity of the inflammation response. The magnetic-bead assay allows a rapid overview
of cytokine profiles specific to each tissue and is an easy method to test the efficacy of medical
countermeasures in a dose and time response manner. The assay was used on GI-ARS samples generated
by MCART studies to observe the effect of high dose X-irradiation on the level and time course of cytokines
present in plasma and different sections of the gastrointestinal tract. Tissue lysates were prepared at a
range of timepoints from 10-12 week old C57Bl/6 mice following 13Gy irradiation. The pro-inflammatory
cytokines IL-6, IL-1β and TNFα were measured alongside the anti-inflammatory IFNg, IL-13 and IL-10.
Within the tissues each cytokine profile was specific and varied with intestinal region, possibly reflecting
the differing kinetcs of ulceration in the small intestine and mid colon, and the flora present and
translocating post irradiation. For example, whilst levels of TNFα rise post irradiation, the response is more
dramatic and sustained in the mid colon compared to the small intestine. It was also clear that the soft
tissue responses differed from that of the plasma. The plasma is likely to integrate the response from
many organs and hence notoriously difficult to interpret and use as biomarker of GI damage. However,
temporal changes in local tissue cytokines may help identify intervention points and pathways for novel
therapies and radiation countermeasures. Furthermore, characterisation of the protein levels, rather than
the mRNA (as is often described) is more representative of the active inflammatory response. Ongoing
studies are investigating the longer term cytokine profiles changes associated with the delayed effects of
acute radiation exposure (DEARE) and links to organ-specific fibrosis. Funded in part by US Federal funds
from NIAID, NIH, and DHHS: Contract No: HHSN272201000046C.
221 | P a g e
