-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-