-9-
in output c5 TSH.
The curcnic stimulating 2Frect cf TSH in tne thyrofd cces sreuuc-
hyperpiasi= and glandular nypertropny whicn -itimaetel,y leass cc unconfrelled grcowtr
of celis i areas of the thyroid. In the rast few years at least twofgrcurs <s5 investigaters (Lindsay and 'rth) have suggestei cnet there may De 4 dobble mechanisz.
responsizis ror radiaticn induced neoplasms; is.: that raciaticn
initflates 7:.. necor_=.
and that TSH promotes its growth. The princiza. investigatcr First
nbtec cellular
bypertrors: (increase in ceil heights in scme <= cxanse's chicks thatphad beer Zive:.
I (published in 1948). This has been cbservec by many investigat S since and re.
been consicered a manifestation of the stimuivs orem TSH, Dut assays or TSH have,
ao
until recently, not been sufficiently sensitive <a detect very sligh
elevations or
ublications <:
of 1311 recher than large ones.
han the most
TSH. We save learned from our own investigaticrs in animals and the
others that neoplasms are sroduced much more ccorsistently Ly surprisi giy sm&il dos==:
We also know <nat, if there is more
subtle evidence of histolcgic damage from +712, =he incidence of neo asms is much <<=creased. In studies published under this contract and former contra S, we have show.
that radiszion from 151] caused intrinsic Gamazs that might impair t e@ Capacity for
cellular replication withcut seriously hamperimz normone troduction.
damage
migc= cause a rise in TSH to significarczl, detectable levels
damage precludes neoplasm development.
The nes< for a very sensitiv¢
obvious lis. an experimentai design to test che surtle
neoplasm <évelopment.
effects that TS
Thus, tco mum.
Hut the degree -TSH assay was
mght have cr
Our collaborative studies with Dr. Rober= csnard and Ercokhaven Naticmal Laborst:r:
of neoplasms =.
on the Mershallese have prompted Serious questicming of the TSH orig
these peccie. Nine years after the 1954 thermonuclear bomb accident the first thyrci:
neoplasm a>peared. When more Marshallese deve_cped nodular goiters, the question wes
raised ccricerning the efficacy of the prophylactic administration of
to inhibiz the development of more neoplasms i>. these people. On t
sensus of opinion, it was elected to give T,. is near as we can te
been taker. rather well and T,, serum levels (at first PBIs) have be
pectable -evel in mst individuals. More recemcly TSH levels in th
determinec. They have rarely been found eleveztad. In spite of the
continuec to find new lesions on almost every =—ual examination of
We have found a total of 6 carcinomas in 28 operations. Adenomatou
in all. “he observations have prompted some s-=Dticism as to wheth
plasms ac whether T, acministration inhibitec =nem. This has beco
animal ex>eriments in the past few years.
hyroid hormone .7_
basis of a ca
» Ty tablets heave
kept at a resserum have bee=-.
observations w=
hese exposed pe=r_change was fount
TSH induced ne=x-
the basis for soc
Radioisr:moassay for TSH and its Applicaticn <2 the Study of NeopJasm Induction
During the past year under this contract w= have instituted ang tested the raci:immmoassay (RIA) for rat TSH in our laborater.. This has been dong according to té
NIAMDD method with assistance of Dr. P. Reed Larsen (formeriy of Pigttsburgh and now
Peter Bresct Brigham Hospital, Beston), who hes =een a collaterator
gn the Marshalles=
work. DIxccing the last few months we feel our zssay has become wellfestablished anc <5
reliable. We are using the NIAMDD Rat TSH: I-: (potency 35 I.U./mgB for lodinaticr.
and Rat TSH RP I-2 for standard. Our range <> normal values in seferal groups tes7==is from +5 to 800 ng/ml with a mean 9f 410 ng‘=_. Experimental anifpals whose thyrcics
had been removed or destroyed with isiy range == hign as 3,500 ng/
One vear ago when more than 100 animals were being sacrificed
a series oF
Yradiatec animals (at 22 months), animals were <mesthetized and exsahginated by direct
heart puzcture. The blood was centrifuged an= the serum frozen unthl the RIA was
fully operational in our laboratory. Informetisn was subsequently Bssembled regaro“-z
the presence of microscopic neoplasms in the =-,roeid, rad‘ dese of 31 originally re-