The Development of Neoplasms in Irradiated Animal and Human Thyroids
From the world wide experience now available, it seems clear that the Bevelopment
of a neoplasm, especially a malignant one, is not a common sequella of 1317] irradiation
to the thyroid in adults. Not enough is known about their occurrence in chpldren
because few children have been so treated. The reports of Sheline, Lindsayland their
associates suggest that the occurrence of nodules following 13 I is considefably more
frequent in children than adults. OthersSsuch as Crile and his associates agd Starr and
his associates have no concern about the possibility of the development of
geoplasms
the doses used are so large and cellular replication so impaired that the
cliances of
in children. Because of continued concern, the mmber of children treated pith ly
remains small. Thus adequate experience is not yet available. Although thd occurrence
of necplasms may be very low following 1511 treatment for hyperthyroidism 14 may be that
neoplasm formation is almost precluded.
The experimental designs of the studies to be described have taken intd consideratiam
several factors about which we mst learn more. 1.) The age at which neoplsms are most
likely to be produced. 2.) The dose of 131] which is sufficiently disruptihg to the
cell to induce abnormal replication but not so great that it destroys the cabacity for
replication. Presumably the most effective doses which produce neoplasms lif between
the equivalent of the tracer dose and the therapeutic dose used in man. 3.)] Determine
what other factors might promote neoplasm formation. 4.) Observe neoplasms during the
early stage of their development and the related features in the remainder of
which are giving rise to neoplasms.
the gland
A number of large series of long-term rat experiments have been set up fiuring
the latter half of this contract to study the development of neoplasms of
thyroid
in rats treated with various doses of
It is well known from our own bxperiments
and those of others that thyroid neoplasms in the raf require more than 4 ear to develop
after continuous administration of a goitrogen or
I. Hence the problem of housing
and the cost of feeding have been seriously limiting factors. In addition,
very large series of animals with many controls has been necessary because of
losses and (in our earlier experience) a rather low incidence of necplasms.
fhe need for
natural
]Far these
reasons and the limitation of funds, only one series of animals has been posgible at a
time.
In the past there has been controversy concerning the ease with which ngoplasms may
be produced in animals with 1317, One of the failings in mst of_the published
experiments designed to test neoplasm formation in animals given 131r has bean the
primary attention to how much of the isotope was given to the animals and nog how much
and how long it was retained. It has become apparent over a long period of qxperimentatia
that the amount retained in the thyroid may be enormously different than that] anticipated
from the amount injected and the variations in the amounts retained amng anifmls may be
very great. As a result we have resorted to individually identifying each arfimal and
Measuring its uptake and retention by in vivo amd in vitro counting. Weighing the gland
of representative animals to determine a mean thyroid weight has contributed [bo the
reliability of calculating rad dose.
The same basic experimental pattern has been followed on 5 series of rat over the
past 10 years. The same strain of Sprague-Dawley Rats from Charles River Brebding
Colony have been used exclusively through the past 5 years. A Remington diet}has been