Dose and Biological Indicators
Levets of Biological Organization
Pair B:
Public Health
populations
Defined populations
and subgroups
Organisms
System-element
Pair A:
Medicine-toxicology
Organs
are used extensively and with a high degree of
precision. Late effects. particularly cancer where
the approach becomes more problematical. will
then be discussed.
Molecules
Fig. 1. Levels of biological organization, which are
both interlocking and recursive. Thus any given level,
e.g., Organ-organism can at once serve as a system,
the vital elements of which are cells (system-element
Pair A), and the elements of a larger system. a defined
human population (system-element Pair B).
that must be known for proper diagnosis and prognosis. In whatfollows, it is the intent to showthat
this approach is the reverse of the historical and
normal course of events in medicine, i.e., it is the
severity of organ effect that is used ultimately for
diagnosis and prognosis. This holds even if the
dose of an offending agent has played a causal
role in the abnormal condition requiring medical
attention. and often even when therapy has been
started with an initial dose of a medicinal agent.
To elaborate, the fraction of organ cells
killed or the number of chromosomeaberrations
in cells can be indicators of the severity of biological effect in the organ. Under proper conditions, one can then use this information as an
indicator of the likelihood that the biological system of interest will respond quantally. Even if a
dose of a causative offending agent has been estimated, there is no need to go backto that dose for
purposes of diagnosis or prognosis. However.
the severity of effect has varying degrees of usefulness. depending upon howclosely the effect
observed can be causally related to the probability of a quantal response of the organ system.
Thus an effort will be made to specify the conditions under which a biological indicator can
a
be directly relevant
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As an initial example. only early acute
effects from and responses to radiation exposure will be used e.g.. early mortality in the
mammal. Here biological indicators must be and
0.90
Toillustrate the normal role of severity of
organ effect in diagnostic medicine, it is first
shown that the usual acute dose mortality
response curve. e.g.. for x- or gammarays delivered to the whole body. can be broken downinto
two separate curves. For the usual curve (Fig.
2). acute mortality in, e.g.. the mouse. the fraction
of animals responding quantally (dying). 1s plotted against the absorbed doseto obtain the usual
threshold. sigmoid function. Thefirst derivative
of this curve yields a gaussian-type distribution.
that is often associated with the distribution of
sensitivities of the individual animals [1]. It 1s
nowwell accepted that the usual 30 day mortality is due to complications resulting from depletion of the stem cell population in the bone
marrow of the animal, i.e.. with reference to
Figure 1. the bone marrowis the system ofinterest. the relevant elements of which are the stem
cells (system-element pair A.1in Fig. 1).
100
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% Mouse Mortality
System-element
Societal or other
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Dose (Gy)
Fig. 2. A conventional dose-quantal response function. tor which the (fractional) number of animais
responding lethallyis plotted against the dose of the
agent. radiation energy {250 kVp x-rays). These data
were derived from mice of the CBA/Ca (BNL) strain.
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