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a.
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Several months Tollowins a modest dose of 131 T to rats anaa
latent pericl 2

which Sew cells can be stimulated to synthesize DNA, a supra-maximal fsurge by -any cet?
synthesizing DNA was produced by stimulating such a gland.

This occurred before many

of the celis had succumbed and the gland had begun to shrink in size.
It was these and other related observations that led to further fexperiments in
which progressively smaller and smaller doses of 131 I were used in large groups of
rats.

With each succeeding experiment which required 2 to 3 years tq@

neoplasms developed.

complete, more

The need for longer periods of observation bec4me apparent.

The neoplasms first began to appear at 14 to 16 months.

When there

fas reasonable

expectation that neoplasms were soon to appear, many animals were sSafrificed and auto-

radiographs were prepared by giving a trace amount of 1 3 ty just befofe sacrifice to
locate sites of fumction and tritiated thymidine (7H-TaR) to locate
thesizing DNA.

Fhe nuclei syn-

With longer periods of waiting, neoplasms in all stapes of develonment

were found and studied.

Three types of lesions commonly seen in these animals were

papillary, follicular and solid cellular.

At least some of the lesions that develop

spontaneously in elderly rats were parafollicular cell (medullary) thype as described
by Lindsay and by Williams.

The remainder of the solid cellular legions were rapidly

growing as implied from the abundant labelling of the nuclei by 33-Far.

The details of the development of the lesions have been descriffed in a manuscript
which was submitted for publication but publication has been delaye@
described later.

When large numbers of animals were sacrificed at

for reasons to be
fhe time neoplasms

could be expected to be developing and thereafter for months, the sfquence of the

development of neoplasms could be studied.

The multicentricity of

f~esions in the sane

animal and the lesions found in multiple animals sacrificed at intervals permittedan
interpretation of the development of the lesions.
cular epithelium.

Papillary lesi

arose from folli-

Occasional follicles several times the diameter Pf the surrounding

normal follicles appeared.

This was the first sign of a localized abnormality develop

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