- 12 -
a.
.
.
.
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