Abstract
In considering the body of radiobiological knowledge upon which the present possibilities for the development of an objective quantitative laboratory procedure for early detection of radiation injury depend, it is evident that there are at least three general categories of radiation effects which are relevant to this objective: (1) Products of the enzymatic-chemical breakdown of macromolecules, and lysis of killed or dying cells from radiosensitive tissues, for example deoxypolynucleotides from lymphoid tissues and bone marrow; (2) Radiation-induced inhibition of synthesis of deoxyribonucleic acid (DNA) and/or other macromolecules, eliciting alterations in tissue and blood concentrations and pool size of metabolic intermediates in the synthesis, for example, deoxycytidine; (3) Radiation-induced alterations, suppression, or cessation of specialized cell function; of particular interest here is the immunological functions of lymphocytes, including those in the circulating blood. For rodents, the exquisite radiosensitivity of bone-marrow-stem cells as well as of lymphocytes has been precisely measured by modern cellular radiobiological techniques: the colony-forming technique of Till and McCulloch, yielding a D{sub 0} for bone-marrow cells of about 80 R; and the graft-versus-host reactivity of transplanted lymphocytes yielding a similar D{sub 0} value. In our own hands, a modified colony-formation technique for dog bone-marrow cells irradiated in.vitro and
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Cole, L. J.
[1]
- Life Sciences Division, Stanford Research Institute, Menlo Park, CA (United States)
Citation Formats
Cole, L. J.
Biochemical and Radiobiological Factors in the Early Detection of Radiation Injury in Mammals.
IAEA: N. p.,
1971.
Web.
Cole, L. J.
Biochemical and Radiobiological Factors in the Early Detection of Radiation Injury in Mammals.
IAEA.
Cole, L. J.
1971.
"Biochemical and Radiobiological Factors in the Early Detection of Radiation Injury in Mammals."
IAEA.
@misc{etde_22192496,
title = {Biochemical and Radiobiological Factors in the Early Detection of Radiation Injury in Mammals}
author = {Cole, L. J.}
abstractNote = {In considering the body of radiobiological knowledge upon which the present possibilities for the development of an objective quantitative laboratory procedure for early detection of radiation injury depend, it is evident that there are at least three general categories of radiation effects which are relevant to this objective: (1) Products of the enzymatic-chemical breakdown of macromolecules, and lysis of killed or dying cells from radiosensitive tissues, for example deoxypolynucleotides from lymphoid tissues and bone marrow; (2) Radiation-induced inhibition of synthesis of deoxyribonucleic acid (DNA) and/or other macromolecules, eliciting alterations in tissue and blood concentrations and pool size of metabolic intermediates in the synthesis, for example, deoxycytidine; (3) Radiation-induced alterations, suppression, or cessation of specialized cell function; of particular interest here is the immunological functions of lymphocytes, including those in the circulating blood. For rodents, the exquisite radiosensitivity of bone-marrow-stem cells as well as of lymphocytes has been precisely measured by modern cellular radiobiological techniques: the colony-forming technique of Till and McCulloch, yielding a D{sub 0} for bone-marrow cells of about 80 R; and the graft-versus-host reactivity of transplanted lymphocytes yielding a similar D{sub 0} value. In our own hands, a modified colony-formation technique for dog bone-marrow cells irradiated in.vitro and in vivo give D{sub 0} values of {approx}100 R. Thus, on the basis of radiation sensitivity and the time-relationships for interphase cell death for lymphocytes, it appears that this cell class is probably the best ''candidate'' source for an early radiation-injury detection system. However,- the important report by Zicha and Buric indicates that extrapolation of biochemical data on radiation dosimetry from rodents to man is not necessarily feasible, at least in the. case of the urinary excretion of deoxycytidine after irradiation, since human liver actively de-aminates deoxycytidine, in contrast to rat liver. Biochemical and immunological tests on peripheral blood lymphocytes removed within hours after radiation exposure may afford a sensitive approach to early detection of radiation injury. Thus, DNA synthesis as measured by the incorporation of tritiated thymidine into .the DNA fraction is drastically inhibited in irradiated rat lymphocytes incubated in vitro, in response to the addition of phytohaemagglutinin. Theoretically, the responses of these easily accessible cells to phytohaemagglutinin and to other selected antigens in vitro should be amenable to quantitation after radiation-dose levels which elicit only minimal lymphopenie effects. Further studies on the molecular basis of these radiation effects on lymphocytes, together with deeper insights into the mechanism by which ionizing radiations initiate the sequence of events leading to the breakdown of DNA and the release of histdnes from nucleoproteins of these cells, are required for the implementation of practical methods for biochemical detection of radiation injury in man. (author)}
place = {IAEA}
year = {1971}
month = {Mar}
}
title = {Biochemical and Radiobiological Factors in the Early Detection of Radiation Injury in Mammals}
author = {Cole, L. J.}
abstractNote = {In considering the body of radiobiological knowledge upon which the present possibilities for the development of an objective quantitative laboratory procedure for early detection of radiation injury depend, it is evident that there are at least three general categories of radiation effects which are relevant to this objective: (1) Products of the enzymatic-chemical breakdown of macromolecules, and lysis of killed or dying cells from radiosensitive tissues, for example deoxypolynucleotides from lymphoid tissues and bone marrow; (2) Radiation-induced inhibition of synthesis of deoxyribonucleic acid (DNA) and/or other macromolecules, eliciting alterations in tissue and blood concentrations and pool size of metabolic intermediates in the synthesis, for example, deoxycytidine; (3) Radiation-induced alterations, suppression, or cessation of specialized cell function; of particular interest here is the immunological functions of lymphocytes, including those in the circulating blood. For rodents, the exquisite radiosensitivity of bone-marrow-stem cells as well as of lymphocytes has been precisely measured by modern cellular radiobiological techniques: the colony-forming technique of Till and McCulloch, yielding a D{sub 0} for bone-marrow cells of about 80 R; and the graft-versus-host reactivity of transplanted lymphocytes yielding a similar D{sub 0} value. In our own hands, a modified colony-formation technique for dog bone-marrow cells irradiated in.vitro and in vivo give D{sub 0} values of {approx}100 R. Thus, on the basis of radiation sensitivity and the time-relationships for interphase cell death for lymphocytes, it appears that this cell class is probably the best ''candidate'' source for an early radiation-injury detection system. However,- the important report by Zicha and Buric indicates that extrapolation of biochemical data on radiation dosimetry from rodents to man is not necessarily feasible, at least in the. case of the urinary excretion of deoxycytidine after irradiation, since human liver actively de-aminates deoxycytidine, in contrast to rat liver. Biochemical and immunological tests on peripheral blood lymphocytes removed within hours after radiation exposure may afford a sensitive approach to early detection of radiation injury. Thus, DNA synthesis as measured by the incorporation of tritiated thymidine into .the DNA fraction is drastically inhibited in irradiated rat lymphocytes incubated in vitro, in response to the addition of phytohaemagglutinin. Theoretically, the responses of these easily accessible cells to phytohaemagglutinin and to other selected antigens in vitro should be amenable to quantitation after radiation-dose levels which elicit only minimal lymphopenie effects. Further studies on the molecular basis of these radiation effects on lymphocytes, together with deeper insights into the mechanism by which ionizing radiations initiate the sequence of events leading to the breakdown of DNA and the release of histdnes from nucleoproteins of these cells, are required for the implementation of practical methods for biochemical detection of radiation injury in man. (author)}
place = {IAEA}
year = {1971}
month = {Mar}
}