RADIATION STANDARDS, INCLUDING FALLOUT

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however, that there is no ground, on the basis of Russell’s data, for concluding
either that the relation of mutation frequency to dose is not one of linear propor-

tionality or for concluding that there is any threshold at very low doses.
In both
of these important matters, the data show precisely the contrary.
For the low

His (penalgee

dose rates, the frequency of mutations still increases linearly with the dose.
There is no indication of a threshold. A total dose of only 86 rcentgens at a low
dose rate produced exactly the expected frequency of mutations.
Efforts to confirm this important finding of a difference in the effects of high
and low dose rates applied to the immature germ cells of the mouse have been
made. Work with Drosophila, carried out by Muller, Oster, and Zimmering,
leaves the issue uncertain because of difficulties in dosimetry, although the first
reports indicated a confirmation of the effect. It is reported that a similar
experiment conducted at Harwell has confirmed the dose rate effect for
Drosophila.
In the mouse it is impossible without vast expense and labor to test the mutation rates for doses much lower than 86 roentgens. For this kind of experiment
we must resort to using a species that can be raised more cheaply and in far
greater numbers, such, for example, as the fruit fly. In my own laboratory
we have recently completely a 3-year study of the mutation frequency produced
by a dose of only 5 roentgens to the mature male and female germ cells. This
represents, I believe, the lowest dose studied for mutagenic effect in any animal
up to this time. During the early days of the Manhattan project a team of
expert geneticists spent several years in pushing the dosage curve for mutation
down, first to 50 roentgens and finally to 25 roentgens. To those levels the dosage
curve was shown to be strictly linear. The present study carries the dose relationship down to a level comparable to that of the normal human 30-year dose
from background radiation. In order to carry out this study, dominant mutations
of a particular minute bristle type occurring at some 60 genetic loci in the chromosomes were resorted to, instead of the usual recessive lethal mutation technique,
which requires breeding a culture for every tested germ cell. In our recent study,
1,360,948 individual flies descended from parents each of which had received
a 5 roentgen dose of X-rays were scored. There were 50 separate replications
of the experiment, each of exactly balanced irradiated and unirradiated control
cultures and each coded so that the scorers were unaware which series had been
irradiated. The number of mutations found in the irradiated series exceeds
that in the controls by slightly more than was originally predicted, on the basis
of the mutation frequency at doses of 1,000 roentgens and above. The difference
is statistically significant, so that one is entitled to conclude that even doses of
5 roentgens produce mutations at a frequency falling right on the linearly proportional dosage curve. There is no sign of a threshold or of diminishing effec:
tiveness.
Sterility, or loss of fertility through killing of germ cells or the production
of dominant lethal effects that kill the offspring, usually at a very early stage
of development, may also represent genetic effects, although they are often not
passed down beyond the immediate progeny of the treated individuals. In the
Drosophila experiments with 5-roentgen doses, just described, it was found that
the immediate parents produced significantly fewer offspring than the unirradiated control parents of the same genetic strain, bred in the same numbers and
under the same conditions. The reduction amounted to slightly more than 1
percent. Even low doses may therefore produce a proportional reduction of
fertility. In mice, however, the situation is quite different, at least in the
female sex. In male mice, following doses of 100 roentgen or more, temporary
sterility results; but after passage of sufficient time for the more sensitive
spermatozoa, spermatids, and cells in the maturation divisions to be replaced
by cells that were in the more resistant spermatogonial (immature) stages
when they were irradiated, fertility is recovered. In female mice, the reverse
is true. After acute radiation, a female mouse may produce one or a few
litters, but even a dose of 50 roentgen leads generally to permanent sterility.
If the radiation is administered at a low dose rate, it takes only a moderate
increase (to 80 roentgen) to produce the same effect. If human females responded to radiation in this way,the sterilizing effect of radiation would be the
most fearful aspect of exposure to fallout and residual radiation among the

survivors of a nuclear attack on a population.

Studies at the Oak Ridge Na-

tional Laboratory by the Russells and their coworkers, especially E. F. Oakberg,
now clarify certain aspects of this situation. Female guinea pigs and hamsters,
as well as monkeys, are much moreresistant than female mice to the sterilizing
effect of radiation. It seems that in the female mice the oocytes in the ovary

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