92

YH SHORTER-TERM BIOLOGICAL HAZARDS OF A FALLOUT FIELD

of deleterious mutations and at the same time
survive with reasonable vigor. The level of the
load carried—genetic guality—-varies naturally
withthe rate at which deleterious mutations are
added to and removed from the gene pool. Tf,

then, it can be said that a stock has been weak-

ened by an excess of deleterious mutations, the

obvious steps for achieving recovery, or reduc-

tion of the load, would be decreasing the rate of

mutogenésis and increasing the rate of removal.
This means lowering exposure to mutogens
like radiation on the one hand, and lessening
the factors conducive to maintenance of the
lesa fit on the other.

In summary, the attempt in this brief paper
has been to consider someof the effects induced
in living systems by radiation from pervasive
sources such as fallout and the kinds of repair
that accompany them. Three types of erosive
effect have been identified: (1) That resulting

from necrosis of growing tissues in individuals
and leading to various forms of cytopenia,

eventual organ failure and death; (2) that
resulting from generalized degenerative change

in growing tissues and culminating in earlier
time of death; and (3) that resulting from

mutational changes in the germ plasm of population groups andleading to loss of group vigor
and stamina. It was pointed out that recovery
in connection with the first consists of tissue”
replenishment—a biological factor; that recovery in connection with the second had no
meaning with respect to mutational changes
but did have in terms of competition between
normal and mutated tissue materials; and that

recovery in connection with the third consisted
of lowering the rate of inducing mutations and
also inereasing the rate at which mutations are
removed from the gene pool.

DISCUSSION
Paul S. Henehaw
Dr. Bonn (Brookhaven).

Y would hike to

RATE OF REPAIR OF RADIATION DAMAGE IN MICE

make a comment on the steepness of the slope

that Dr. Henshaw presented that presumably
applies to human beings. I cannotcertainly
argue with this slope, because I know of no
definitive data on human beings that would
allow us to define this. However, I would like
to say that the slope for most mammals that
have been studied is considerably steeper than
the slope indicated by Dr. Henshaw. The
factor that would apply in his case in his curve
in going from LD-zero to LD-50 would be
about two. In most mammals this factor is
about1.2.
Dr. Beran. Thenk you, Dr. Bond. Is
there any other discussion? Dr. Henshaw?
Dr. Hensuaw.
My main experience has
been with laboratory animals also. When I
began to consider this question, I, too, had in
mind that the time intervals involved, and

indeed the slope of the curves presented, would

be somewhat different from this picture as
presented. But in asking these questions in

relation to human beings and taking the frag-

ments of information as we are able to get them

from those who have had experience in con-

nection with the Japanese damage, the few
radiation accidents, and some other kinds of
considerations, the indications are that the time
intervals involved are longer in the case of

human beings than in the usual laboratory
animals, like rats and mice.

So I concur completely with the implications
of the question that was raised.

By Joun B. Srorer

Los Alamos Scientific Laboratory, University of C‘alifornia, Los Alamos, New Merico

In the following study tho repair rates of

tissues exposed to ionizing radiation were not

measured directly,

Rather, the rate of repair

where R,=percent of initial damage (or dose)
remaining at time ¢
D,=initial dose in r
LDyo, TDyp dose at. time ¢
LDoe= Dy dose for controls

of damage contributing to the death of mice by

two different mechanisms was determined,

The end-points used were median lethal dose

for death in the first 30 days following exposure

(LDj-30 days) and the medianlethal close for
death in the first 100 hours after exposure
(LDg-100 hours). In the ease of X-radiation
exposure, deaths occurring in the first 100 hours
are generally due to radiation damage to the
gastrointestinal tract (in the doserange below
10,000 r). The later deaths associated with
the LD,»-30 days are believed due primarily to
hematopoietic damage. Thus, it was possible
to measure indirectly the rate of repair of two
radiosensitive organ systems.
The split-dose technique as described by a
number of authors was used. Large groups of
mice were exposed to an initial sublethal dose
of X-rays and at various time intervals there-

after they were divided into subgroups and

given graded doses of X-rays in order to deter-

mine the LDj»-30 days or LDy-100 hours. The
extent to which the LD was lower than the

value for the control group then gave a measure

of the amount of the damage remaining from
the first exposure. This residual was necessarily measuredin roentgens but since the dam-

age is proportional to dose, this system of
measure is probably sound. The residual was
then converted to percent. of initial damage by

dividing “residual roentgens” by
roentgens” and multiplying: by 100.
Thus:
LDg,—LD.

“5 X10

“initial

Female CF.--1 mice, 2-3 months of age, were
used throughout these studies. X-rays were
delivered from a G. E. Maxitron operated at 250

KVP and 30 Ma.
added.

A Thoraeus I filter was

HVLof the filtered beam was 2.6 mm

Cu. Mice were exposed 15 at atime in a shallow

Lucite cage curved on a radius of 50 cm. The
TSD was 50 cm.
In the study utilizing 30-daylethality as the
biological end-point, groups of mice were exposed to aninitial dose of 100, 200 or 400 r, At

intervals of 4, 8, 18, 32, 72, 144, 264,504, 1,920,

or 3,000 hours, the LDj-30 days was determined in groups of these mice and(at similar intervals) in control mice from the same initial

population. The results are shown in Table I.

A plot of these data showed that. the best empirical fit to a regression line was obtained when

percent residual was plotted as a function of log
time. The least squares calculation gave an
equation

Y= 106.03 26.79 log X

where ¥ is percent residual and X is time in
hours. This line and the experimentally determined points are shownin Figure 1.

It is apparent from this line that, over the

range of doses tested, the percent residual injury
was independent of dose. Since this type of

exponential is difficult to integrate into a biological model for the repair process, the data
98

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