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Dose, Effect Severity, and Imparted Energy in Assessing
Biological Effects

) threshold theory of
ihaled radon energy
995-68 :157-174.

Brookhaven National Laboratory, Medical Department, Upton, New York. USA


V. P. Bond

Key Words. Cancer ¢ Absorbed dose * Imparted energy ¢ Severity of effect « Quantal biological response
* Medicine versus public health
Abstract. Because of the widespread efforts in cancer radioepidemiological studies to attach a value
of absorbed dose to each exposed individual, the
notion seems to have become prevalent that dose
plays an essential role in the medical determination
of the diagnosis and prognosis of the individual.
This view is enhanced by the fact that, while the
present quantities and units for radiological physics
were developed in the contextof the acute effects of
large exposures to radiation, e.g., in radiotherapy
wherethey still apply well, these same quantities
and units have been used, without modification, to

apply to cancer radivepidemiology in the context of
low level irradiation. A principle purpose of the present communication is to show that, in medicine,
dose plays a limited role even in the deterministic
application of therapeutic agents, and that diagnosis
and estimates of prognosis in medicine are based,
not on dose, but on the severity of effect on, or dam-

age to the organ or organs involved in a particular
medical condition. Thusit is “going backward”to
view estimates of the severity of effect, e.g., the fraction of cells with abnormalities, or killed, as a “bio-

logical dosimeter,” rather than as a quantitative
estimate of the severity ofeffect.
The use of biological indicators is of maximum value in noncancerousdisease or injury in
which the severity of an effect causative for organ
failure and a consequent quantal, e.g., a lethal
responsein the individual, can be measured with
increasing accuracy by modern medical techniques.
A commonscale for the measurementof almost
any typeof effect on any organis 0.0 to 1.0 (0.0 to
100%), with 100% meaning complete functional
failure and certain death if the organ is vital. The
opposite extreme is cancer, in which, particularly
Correspondence: Dr. Victor P. Bond. Medical
Department. Brookhaven National Laboratory, P.O.
Box 5000, Upton, NY 11973-5000, USA.
Received November 21, 1994; accepted for publication November 21, 1994. ©AlphaMedPress 10665099/95/35 .00/0




LZ ‘| GO STEM CELLS 1995313(suppl1):21-29



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with low level irradiation, there is no detectable

effect directly relevant to cancer causation. the
severity of which will provide an individualized,
medical-type diagnosis or prognosis. However, this ~
situation is beginning to change with the rapid
development of molecular biology and genic change
profiles that may make individualized prognostic
estimates possible. However, because neither radiation nor other carcinogens leave “markers,’”’ the
impact of these changes with respect to lowlevel
irradiation must be left open.


Before biological effects and responses of
any kind can be assessed objectively, it 1s necessary to review and discuss the various levels of
biological organization at which these can occur.
In Figure 1 is shown a numberof levels, most
of which are both interlocking and recursive.
This means that most of the levels can be
regarded as a potentially responding system,
composed of potentially damaged elements
located one or more levels lower on the scale.

However, it also means that the identical level
can be regarded as a population of elements,

severe damage to which may cause a quantal
response in their parent system located one or
more levels higher up onthescale.
In the past, when the dose to a system has
been unknownor only poorly known, an observable biological endpoint such as chromosome
aberrations in cells, has been used frequently
as a “biological dosimeter.” In other words,
because the numberof cells with a given aberration determined in an individual is a function
of dose, a given level of response can be used
to obtain an estimate of the dose received. The

implication is thatit is the dose to the individual

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