-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

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