Page 22 - 2014 Printable Abstract Book
P. 22
9/11 there has been a push by several government entities to find remedies that can be given to
populations after the exposure and without necessarily knowing the exposure dose. Because of standard
guidelines for chemically or biologically derived drugs that can be prescribed for human use these research
efforts have been focused on producing new molecules that can be given to humans. In this topical review
we examine how, as the molecular pathways that radiation exposure both induces and interferes with
have come to light, they have led researches to examine possible new routes to mitigate the effects of
radiation. In particular there is a push to develop small molecules based on biological pathways that will
dampen or eliminate deleterious effects of radiation. Remarkably there are now several compounds
emerging that can reduce the effects of radiation in the skin, the hematopoietic system and in mucosal
surfaces such as in the intestines and lining of the mouth and throat when given after the radiation
exposure. The review will examine some of the pathways being studied that offer potential for
intervention including inflammation, apoptosis and cell replacement with examples of some promising
data. But there are also possible pitfalls that must be overcome to ensure FDA approval of some of these
molecules. Some molecules are believed to either recruit or reactivate resting stem cells to sites of
damage and others prevent cell death. It will be important that preventing cell death or replacing dead
cells with new ones does not increase risk of cancerous events or degenerative diseases later in life, as a
result. There is much promise, but can we mitigate radiation exposure safely or do we allow some risk for
a lot of benefit (survival) in the short term.
TR14. TUMOR OXYGENATION AND THE RADIATION RESPONSE
1
(TR1401) Tumor Oxygenation and the Radiation Response. Harold M. Swartz, MD, PhD ; Ann Flood,
2
1
1
PhD ; Benjamin Williams, PhD ; and Steven Swarts EPR Center for Viable Systems, Lebanon, NH and U.
1
2
of Florida, Gainseville, FL
There are two critical time points when accurate and timely measurements of acute exposures
are needed: (1) for initial point-of-care screening of a large population at risk of prior radiation exposure,
to triage them in or out of immediate care, and (2) at the next stage, when decisions on management of
individual patients with potential for ARS would benefit from knowing the level of exposure and
whether the body received homogeneous exposure. The principle of biodosimetry is to utilize changes
induced in the individual by ionizing radiation to estimate the dose and, if possible the biological
consequences of the dose. There are two basic types of biodosimetry with different and often
complementary characteristics: those based on changes in biological parameters such as gene
activation or chromosomal abnormalities and those based on physical changes in tissues (detected by
techniques such as EPR). The biologically based parameters are potentially very sensitive to dose levels
and to the biological implications of the dose in the individual. They may require time for assessment
because they require biological processing before changes can be observed and may be affected by other
perturbations that may be associated with an acute event including stress, wounds, and burns. These are
especially likely to be useful for the second stage of triage in which decisions are made regarding
treatment. The physically based methods are not subject to these limitations, hence can be
used immediately after the event. They are especially applicable for initial triage and may also have an
important role in determining the homogeneity of the exposure and therefore aid in decisions as to the
need for treatment. EPR-based biodosimetry using radiation-induced free radicals has now developed
such that it can meet the needs for initial triage (i.e. >2 Gray) and may also provide sufficient dose
20 | P a g e
populations after the exposure and without necessarily knowing the exposure dose. Because of standard
guidelines for chemically or biologically derived drugs that can be prescribed for human use these research
efforts have been focused on producing new molecules that can be given to humans. In this topical review
we examine how, as the molecular pathways that radiation exposure both induces and interferes with
have come to light, they have led researches to examine possible new routes to mitigate the effects of
radiation. In particular there is a push to develop small molecules based on biological pathways that will
dampen or eliminate deleterious effects of radiation. Remarkably there are now several compounds
emerging that can reduce the effects of radiation in the skin, the hematopoietic system and in mucosal
surfaces such as in the intestines and lining of the mouth and throat when given after the radiation
exposure. The review will examine some of the pathways being studied that offer potential for
intervention including inflammation, apoptosis and cell replacement with examples of some promising
data. But there are also possible pitfalls that must be overcome to ensure FDA approval of some of these
molecules. Some molecules are believed to either recruit or reactivate resting stem cells to sites of
damage and others prevent cell death. It will be important that preventing cell death or replacing dead
cells with new ones does not increase risk of cancerous events or degenerative diseases later in life, as a
result. There is much promise, but can we mitigate radiation exposure safely or do we allow some risk for
a lot of benefit (survival) in the short term.
TR14. TUMOR OXYGENATION AND THE RADIATION RESPONSE
1
(TR1401) Tumor Oxygenation and the Radiation Response. Harold M. Swartz, MD, PhD ; Ann Flood,
2
1
1
PhD ; Benjamin Williams, PhD ; and Steven Swarts EPR Center for Viable Systems, Lebanon, NH and U.
1
2
of Florida, Gainseville, FL
There are two critical time points when accurate and timely measurements of acute exposures
are needed: (1) for initial point-of-care screening of a large population at risk of prior radiation exposure,
to triage them in or out of immediate care, and (2) at the next stage, when decisions on management of
individual patients with potential for ARS would benefit from knowing the level of exposure and
whether the body received homogeneous exposure. The principle of biodosimetry is to utilize changes
induced in the individual by ionizing radiation to estimate the dose and, if possible the biological
consequences of the dose. There are two basic types of biodosimetry with different and often
complementary characteristics: those based on changes in biological parameters such as gene
activation or chromosomal abnormalities and those based on physical changes in tissues (detected by
techniques such as EPR). The biologically based parameters are potentially very sensitive to dose levels
and to the biological implications of the dose in the individual. They may require time for assessment
because they require biological processing before changes can be observed and may be affected by other
perturbations that may be associated with an acute event including stress, wounds, and burns. These are
especially likely to be useful for the second stage of triage in which decisions are made regarding
treatment. The physically based methods are not subject to these limitations, hence can be
used immediately after the event. They are especially applicable for initial triage and may also have an
important role in determining the homogeneity of the exposure and therefore aid in decisions as to the
need for treatment. EPR-based biodosimetry using radiation-induced free radicals has now developed
such that it can meet the needs for initial triage (i.e. >2 Gray) and may also provide sufficient dose
20 | P a g e
