Page 87 - 2014 Printable Abstract Book
P. 87
investigating the top 10 loci that predict for radiation sensitivity, which include some DNA repair genes,
but also include genes that do not appear to have a function in the nucleus. Gene editing in iPS cells is
now planned to observe whether the observed associations can be directly validated. Clinical outcome
datasets are available to observe whether these genetic predictors of radiation sensitivity have
prospective meaning. The hope is that epidemiologic data can stimulate interest clinical response to
radiation and that basic radiobiologic studies and clinical datasets may help identify genetic factors which
direct long-term effects in populations.
(S2304) Integrating basic biology and epidemiology: closing the gap for risk assessment. Julian Preston,
US Environmental Protection Agency, Research Triangle Park, NC
Current attempts to estimate the cancer and non-cancer risks of radiation exposure at low doses
(<100mGy) and low dose rates (<5mGy per hour) has resulted in significant uncertainties. One solution to
address this uncertainty is to make fuller use of available basic biology data to enhance the quantitation
of effects at low doses and dose rates. This type of approach has been used in risk assessment for
environmental chemicals for which epidemiology data is nearly always absent. The basic approach is to
develop a biologically-based dose response (BBDR) model by using the components of a so-called adverse
outcome pathway (AOP) as potential parameters for a BBDR model. An AOP framework is considered to
be a logical sequence of key events or processes within biological systems which can be used to
understand adverse effects for use in refining the current risk assessment practice. This approach shifts
the risk assessment focus from traditional apical endpoints to the development of a mechanistic
understanding of the effect of an exposure at the molecular and cellular level for predicting disease
outcome. An example is provided by Adeleye and colleagues for a DNA damage response pathway
mediated by the p53 response using quercetin as a model compound. A set of informative pathway
biomarkers were identified that were, as a set, deemed to be predictive of the adverse outcome. In this
way such biomarkers can be considered as key events. A similar approach can be taken for radiation
exposures, similarly using DNA damage as the AOP. In this way research can be targeted towards the
selection of informative bioindicators of the studied adverse health outcome and not simply markers of
radiation effects. The overall aim is to make these key events quantitative for the prediction of adverse
health outcomes. This aim has been addressed in a so-called Q-KEDRF approach (Simon and colleagues)
for chemical exposures. This general approach can be applied also to the estimation of radiation-induced
cancer at low doses and dose rates based on the current knowledge of key events for the development of
these cancers. It is possible that a similar approach could also be used for non-cancer effects. (The views
expressed here are not necessarily reflective of Agency policy).
S24 EDUCATION AND TRAINING NEEDS IN THE RADIATION SCIENCES: PROBLEMS AND POTENTION
SOLUTIONS
A shortage of adequately-trained radiation scientists will hinder new developments in the clinic & the
response to a radiological disaster. But a vicious cycle exists between preparedness & training; mentors
without proper training cannot teach the next generation of students & physicians adequately. Solutions
to this conundrum will be discussed.
85 | P a g e
but also include genes that do not appear to have a function in the nucleus. Gene editing in iPS cells is
now planned to observe whether the observed associations can be directly validated. Clinical outcome
datasets are available to observe whether these genetic predictors of radiation sensitivity have
prospective meaning. The hope is that epidemiologic data can stimulate interest clinical response to
radiation and that basic radiobiologic studies and clinical datasets may help identify genetic factors which
direct long-term effects in populations.
(S2304) Integrating basic biology and epidemiology: closing the gap for risk assessment. Julian Preston,
US Environmental Protection Agency, Research Triangle Park, NC
Current attempts to estimate the cancer and non-cancer risks of radiation exposure at low doses
(<100mGy) and low dose rates (<5mGy per hour) has resulted in significant uncertainties. One solution to
address this uncertainty is to make fuller use of available basic biology data to enhance the quantitation
of effects at low doses and dose rates. This type of approach has been used in risk assessment for
environmental chemicals for which epidemiology data is nearly always absent. The basic approach is to
develop a biologically-based dose response (BBDR) model by using the components of a so-called adverse
outcome pathway (AOP) as potential parameters for a BBDR model. An AOP framework is considered to
be a logical sequence of key events or processes within biological systems which can be used to
understand adverse effects for use in refining the current risk assessment practice. This approach shifts
the risk assessment focus from traditional apical endpoints to the development of a mechanistic
understanding of the effect of an exposure at the molecular and cellular level for predicting disease
outcome. An example is provided by Adeleye and colleagues for a DNA damage response pathway
mediated by the p53 response using quercetin as a model compound. A set of informative pathway
biomarkers were identified that were, as a set, deemed to be predictive of the adverse outcome. In this
way such biomarkers can be considered as key events. A similar approach can be taken for radiation
exposures, similarly using DNA damage as the AOP. In this way research can be targeted towards the
selection of informative bioindicators of the studied adverse health outcome and not simply markers of
radiation effects. The overall aim is to make these key events quantitative for the prediction of adverse
health outcomes. This aim has been addressed in a so-called Q-KEDRF approach (Simon and colleagues)
for chemical exposures. This general approach can be applied also to the estimation of radiation-induced
cancer at low doses and dose rates based on the current knowledge of key events for the development of
these cancers. It is possible that a similar approach could also be used for non-cancer effects. (The views
expressed here are not necessarily reflective of Agency policy).
S24 EDUCATION AND TRAINING NEEDS IN THE RADIATION SCIENCES: PROBLEMS AND POTENTION
SOLUTIONS
A shortage of adequately-trained radiation scientists will hinder new developments in the clinic & the
response to a radiological disaster. But a vicious cycle exists between preparedness & training; mentors
without proper training cannot teach the next generation of students & physicians adequately. Solutions
to this conundrum will be discussed.
85 | P a g e
