Page 78 - 2014 Printable Abstract Book
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compared to non-CT scanned mice (p < 0.05). In mice treated with the multiple CT scans following the
high cancer-inducing 4 Gy dose, lifespan was increased by approximately 8% compared to mice exposed
to 4 Gy-alone (p < 0.017). We conclude that repeated CT scans can reduce the cancer risk of a prior high-
dose radiation exposure, and delay the progression of specific types of radiation-induced cancers in
Trp53+/-mice. This work shows that clinical diagnostic doses may not pose risk to patients and may have
therapeutic potential to slow cancer progression. We are testing this postulate in patients with recurrent
prostate cancer to assess if repeated low dose half-body exposures can slow or eliminate the disease.
(S2002) Adaptive responses: implication for low dose exposures. Marianne B. Sowa, PhD, Pacific
Northwest Natinals Laboratory, Richland, WA
In the field of toxicology, it is well known that a low dose of an agent may have a beneficial effect even if
high dose exposures are toxic. However, for radiation exposures, it has been assumed that every
ionization that occurs is detrimental and that the damage produced in linearly linked to adverse health
effects. Recent studies have demonstrated that the processing of radiation-induced damage and the
system level response to radiation in the low dose region is non-linear and the system has the potential
to adapt to subsequent stress. This is collectively referred to as the adaptive response. The adaptive
response comes in two forms. The first is when a low dose of radiation is given before a high dose and the
subsequent biological response to the high dose is markedly reduced. The second type of adaptive
responses is observed when a low radiation dose decreased the biological response to a level below the
normal background. This second type of adaptive response may actually be more important in terms of
human health risks as it suggests low doses can be protective against many biological changes induced by
other types of exposure as well as from the genetic background that may be involved in the induction of
disease. We have investigated the low-LET adaptive response and other non-targeted effects in human
colon carcinoma cells. We did not see any evidence of adaption following either an X-ray or electron
microbeam priming dose. However, our results are not surprising due to the high level of variability
observed in adaptive responses, depending both on the individual donor and cell line tested. The
observation of a null result raises the important question regarding the bias of scientific literature towards
positive resuIts. We will discuss this and the relevance of adaptive responses are for human exposures.
This work was supported by the DOE Low Dose Radiation Research Program.
(S2003) Radioadaptive responses and radioprotection in prostate cancer treatment - a pre-clinical
approach. Pamela J. Sykes, Flinders University and Medical Centre, Bedofrd ark, Australia
Low dose radioadaptive responses have been demonstrated in animal studies to increase life-span, reduce
DNA damage, increase cancer latency, and decrease severity of other disease endpoints. These studies
have indicated the potential to harness the adaptive response for translation into the clinic, however more
focused pre-clinical studies are required before clinical trials are likely to be designed. One potential use
of the low dose radioadaptive response is to protect normal tissue during high dose radiotherapy for
localized prostate cancer. High dose radiotherapy can be highly effective at killing prostate tumor cells
but even with image modulated radiotherapy there is still scatter to surrounding normal tissue that can
lead to short and long-term debilitating side-effects including pain, bleeding, erectile dysfunction, and
urinary and bowel incontinence. Protection of normal tissue during radiotherapy has the potential to not
76 | P a g e
high cancer-inducing 4 Gy dose, lifespan was increased by approximately 8% compared to mice exposed
to 4 Gy-alone (p < 0.017). We conclude that repeated CT scans can reduce the cancer risk of a prior high-
dose radiation exposure, and delay the progression of specific types of radiation-induced cancers in
Trp53+/-mice. This work shows that clinical diagnostic doses may not pose risk to patients and may have
therapeutic potential to slow cancer progression. We are testing this postulate in patients with recurrent
prostate cancer to assess if repeated low dose half-body exposures can slow or eliminate the disease.
(S2002) Adaptive responses: implication for low dose exposures. Marianne B. Sowa, PhD, Pacific
Northwest Natinals Laboratory, Richland, WA
In the field of toxicology, it is well known that a low dose of an agent may have a beneficial effect even if
high dose exposures are toxic. However, for radiation exposures, it has been assumed that every
ionization that occurs is detrimental and that the damage produced in linearly linked to adverse health
effects. Recent studies have demonstrated that the processing of radiation-induced damage and the
system level response to radiation in the low dose region is non-linear and the system has the potential
to adapt to subsequent stress. This is collectively referred to as the adaptive response. The adaptive
response comes in two forms. The first is when a low dose of radiation is given before a high dose and the
subsequent biological response to the high dose is markedly reduced. The second type of adaptive
responses is observed when a low radiation dose decreased the biological response to a level below the
normal background. This second type of adaptive response may actually be more important in terms of
human health risks as it suggests low doses can be protective against many biological changes induced by
other types of exposure as well as from the genetic background that may be involved in the induction of
disease. We have investigated the low-LET adaptive response and other non-targeted effects in human
colon carcinoma cells. We did not see any evidence of adaption following either an X-ray or electron
microbeam priming dose. However, our results are not surprising due to the high level of variability
observed in adaptive responses, depending both on the individual donor and cell line tested. The
observation of a null result raises the important question regarding the bias of scientific literature towards
positive resuIts. We will discuss this and the relevance of adaptive responses are for human exposures.
This work was supported by the DOE Low Dose Radiation Research Program.
(S2003) Radioadaptive responses and radioprotection in prostate cancer treatment - a pre-clinical
approach. Pamela J. Sykes, Flinders University and Medical Centre, Bedofrd ark, Australia
Low dose radioadaptive responses have been demonstrated in animal studies to increase life-span, reduce
DNA damage, increase cancer latency, and decrease severity of other disease endpoints. These studies
have indicated the potential to harness the adaptive response for translation into the clinic, however more
focused pre-clinical studies are required before clinical trials are likely to be designed. One potential use
of the low dose radioadaptive response is to protect normal tissue during high dose radiotherapy for
localized prostate cancer. High dose radiotherapy can be highly effective at killing prostate tumor cells
but even with image modulated radiotherapy there is still scatter to surrounding normal tissue that can
lead to short and long-term debilitating side-effects including pain, bleeding, erectile dysfunction, and
urinary and bowel incontinence. Protection of normal tissue during radiotherapy has the potential to not
76 | P a g e
