Dose and Biological indicators

one or both of these genes permits one to say
that the patient has a definitely increased probability of developing the disease. or already has
it. Similar findings may become available with
respect to other malignancies. e.g.. breast cancer
in women. Although it is beyond the scope of
this paper to deal with the progress that is being
madein this area (see other papersin this symposium). the approach of course has the potential
of completely altering the situation with respect
to being able to provide an individual-specific
(1.e.. medical) severity of effect diagnostic and
prognostic probability.
Anaddedproblem exists with respect to the
Causative agent. be it radiation or otherwise. With
cancers and radiation. the criterion for radiation
causation has been the appearanceofthe disease,
€.g.,a given form of cancer, in excess numbers
among the atomic bomb survivors. Whatcriteria for an agent being causative or contributory is

to be used in general for diseases other than can-

a wher

8

cer and agents other than radiation?
As noted above, markers such as chromosomal abnormalities have been used to give
someindication of the dose of radiation received
by individuals. and in the population. However.
there has been little correlation between the type
and-number of chromosomal aberrations tn any
given individual. and the probability of that
individual developing cancer.
In the context of the atomic bombsurvivors,
both the incidence of radiation attributable cancers and persistent chromosomalchanges such as
reciprocal translocations have been studied
(T. Strawme, personal communication). In Figure
7 is shown a plot of both the excess incidence
of reciprocal translocations in bone marrowcells
and the incidence of leukemia. as a function of
the estimated DS86 dose. One can seethat.
although the relationshipis initially curvilinear.
the chromosomal aberration incidence tracks
very closely the estimated dose. Thus. as
expected (Fig. 8). the incidence of cancer (shown
for solid tumors only). is a linear function of the
“severity of effect” as indicated by the numberof
reciprocal translocations.
This approach is useful, because it does have
the advantages noted above in connection with

Su;z24a|

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é

,

'

Excess leukemia cases/10,000 PY

of which one maybe inherited. Thus. finding

0.3

Fraction cells with aberrations

associated diseases. A notable exceptionis
retinoblastoma. which requires two gene changes

Relationship between incidence of aberrations and leukemia
(both cities combined)

t

.

/

Aberrations

DS&6 dose. Gy

Fig. 7. Plot showing howwell both the fraction of cells
with chromosomal aberrations and the excess leukemia
incidence track the dose to the atomic bomb survivors.

particularly in the dose region up to about 1.5 Gy.

noncancer diseases. 1.e.. the relationship is essentially independent of LET. dose rate and shape of
the original dose-response curve. However. this
use of “biological markers” cannot in any way
be compared to their high precision use.
described above, with noncancer disease. The
principal reasonis that. while chromosome aberrations are due to intracellular DNA changes.
and while their increase may well be proportional
to whatever gene change or changes maybe

directly causative with respect to a given cancer. neither the fraction of cells with at least one
observable chromosomal aberration. northe total
Relationship between incidence of solid tumors and chromosome
aberrations in A-bormb survivors (both cities combined)
7.0

y = 5.3309e0-2 + 7.2687x R*2 = 0.964

Excess relative risk
(irom Thompson et al. 1994)

However. few successes have been achieved
to date. and these not with radiation-ex posure

o.8

0.0

r

o.03

o.1

T

2.15

o.2

Fraction of cells with aberrations
(estimated trom data in Preston et al. 1989)

Fig. 8. Pilot showing the linear relationship between
the fraction of cells with chromosomal! aberrations
and the excess relative risk of solid tumors.

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