-5forms were present, but not abundant in the extranodular tissge
thyroid.
A copy of the manuscript describing these findings
of this
gnd entitled
"DNA Content Associated with Nuclear Changes in 1511 Radiated|Human
Thyroids" was submitted to the
Journal of Clinical Endocrinoldgy and
Metabolism and is attached to this report.
Our experimental results in snimals suggest that there is
dose range
of 13ly which for a time after the radiation is given, neitheg completely
destroys the function of the thyroid cell, nor interferes witl|
of those cells to multiply and make a larger gland. After a
the capacity
Jonger lapse
of time and long after the dose of 1311 is dissipated, a defedt develops
in the ability of the radiated cell tc divide, although DNA may build up.
Clinical observations in the husen show that although the subfle damage may
be caused to the thyroid cell, it continues to survive and maMe thyroid
hormone maintaining the individual in ea euthyroid state.
Suparficially, it
may appear that an ideal euthyroid state is achieved in such
clinical
subject. In fact, the euthyroid state psreists for a good many years.
However, we now are beginning to observe at 12, 15 and more
years after
131I therapy thet these husan glands, which appeared to have
alec
capacity to manufacture hormone, ultimately begin to fail and ithe
begins to suffer from hypothyroidiem.
This has become apparent
indfvidual
from our
long term study of these patients. It is thus a reasonable
assumption from
the animal experiments that the expected nonnal replacement off thyroid cells
is not taking place and explains the ultimate failure of the thyroid.
A
Study
of Nucles
Lnanges &
I in Rat Thyroids
»
Time
of
Neoplasm
Formation
Following
Since we know that neoplasms sometimes develop in rat thyrods following
small doses of 1317, and since the frequency of the occurrence] of these
tumors is enhanced by giving thiouracil, it has seemed epproprgsate to use
the tritiated thymidine technique to observe the behavior of thyroid nuclei
as tumors are begiming to develop.
We have in progress two rather extensive experiments on thel frequency of
individual cells forming DNA at various intervels of time during which
neoplasme may be expected to be developing. The purpose is tojwatch the
development of changes in DNA formation in a population of radjated thyroid
cells. A rate of mitotic activity should be manifested by upteke of
tritiated thymidine.
After a brief period of iodine deficient diet to insure a high uptake
of 1311, a large series of approximately 100 rats were injecteq
5, 10, or 50 pe of 1351z, Others received ncee.
with either
Following the]1311 and
a brief respite, chronic administration of thiouracil in the d#inking water
was begun in some rats at each radiation dose level. ‘This serjes of rats
were pubescent and weighed 120 to 140 grams when 1311 was gives. Another
large series of rets which were somewhat younger and weighed f#om 80 to 100 g
grems were prepared with similar doses some months following tile above
series. Representatives of the various groups were killed soon after 1317
was given to determine the actual uptake of
1511 in the averaga gland.
Rats representing the various experimental groups were subdivided following
13ly so that in addition to thosewhich received thiouracil
dnically,
others received it acutely shortly before sacrifice, and still bothers
received none. Each animal was given tritiated thymidine four fhours before
sacrifice, so that contact radioautographs might be made to determine which