Many collateral observations were made on these first two series df animals in
the course of studying the development of neoplasms. Early sacrifices Fonfirmed our

former observation that there is a temporary loss of mitotic activity shortly after

I is given as we previously reported. The abnormally large pupber af mitoses which
appear when goitrogen was given during the recovery phase from
I ocd
ed again.
Although neoplasms do not become manifested until much later, it may bel that they
started at this time.

In a third series of animals, the age at which 1317 was given was bven lower being
28 days; 40 to 65 grams. Althcugh a period of iodine
icient diet wap again used, tr

uptake was 25 to 60% of dose, and the graded doses of

I were reduced so that 5000 tc

200,000 rads were delivered to the thyroid, using 5 dose levels. A tothl of 19 animals
developed neoplasms. Although the number of animals that developed tumpbrs seems small,
it mist be kept in mind that many were sacrificed before one year and thmors were seldc
found before 14 months. Only 25 animals were allowed to survive after 24 months; 12 of
these ultimately proved to have neoplasms.
A 4th large series of animals was prepared. Since the yield of nebplasms had
increased by giving the 1311 at a younger age in the preceeding series,] this present
rinineeneetadnnber de “Seertnh str.seulewnedinniairnians eeetel bps teas:

day.

There were 120 offspring.

by intraperitoneal injection.

Ninety of these were given

31I on

the] 16th day of lif

Thirty serve. as various kinds of controis.

Males und

Females were separated after weaning. Iodine deficient diet could not fe used here.
The actual rad dose delivered to these animals ranged from 300 to 17,00P rads, based on
an average thyroid weight of 7 mg. Since the neoplasms tended to appeap more often in
the lower dose range in the preceeding group of animals, lower doses we
used here.
Furthermore, these thyroids were extremely small, so that considering
ep range of the
beta ray relatively more of the beta radiation caused ionization outsidp the gland.

A

total of 29 discrete neoplasms were found in this series. One of the nh radiated
controls given thiouracil chronically developed a neoplasm. There were] 8neopiasms in
animals that received only radiation and 20 had been given radiation an
thiouracil . Only 49 aninsls were permitted to live longer than 12 months;22
of these
had neoplasms when sacrificed. Most of the neoplasms that developed wifhout the stim
of thiouracil cccurred in the 7,000 to 17,500 rad dose range.
Many collateral observations have been made on these series of animals. Since
tritiated thymidine radioautographs have been made on all thyroids in tlese 4 series,
there is a great deal of information that is just now being appreciated retrospectively
Some of these observations are as follows: Upon reviewing the non-radid*ed control
animals killed at each period of sacrifice it was found that when the qung animals are
given a 5 day course of thiouracil, the degree of rise in mitotic index|(mmber of
.

labeled cells per high power field) is quite remarkable. The young unsfimulated contro.
animals showed 0.5 to 1.6 labeled nuclei while those given thiouracil
sHowed 14.0 to
35.0 per high power field. In contrast the same observations on resting animals 1% to

2 years of age may reveal only one or two labeled muiclei in several crogs sections of a
whole thyroid lobe. When the latter are stimulated under the same cordjtions the maxim
number of nuclei labeled may be less than one per high power field.
For doses of 2300 to 2800 rads, slight temporary impairment to mitdtic activity
occurred but ultimately a maximal wight of thyroid could be produced
chronic thic

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