observed in this patient included not only serious deviation firom the chromosomes but numerous breaks, deleticns and fragmentations (see attached Occasionally dicentric forms were observed and several examples of 4n nucl reduplication of chromosome sets, but without the exact number of 92. Thesa@ nuclei were presumably similar to those seen in the thyroids which built up excess but failed to divide following 1317. DNA These observations were the first re ¢ yntry on chromosomal anomalies in circulating leukocytes of patients trea I. Macintyre, M. N., and Dobyns, B.M.: Anomalies in Chromosomes of the Ci Leukocytes in Man Following Large Doses of Radioactive Iodine. J. Clin. Metab. 22: 1171-1181, 1962. One of the most important parts of these chromsome observations was an 18% incidence of anomalies was found in the circulating leukocytes of blood before the large treatment dose of 131] was given. Presumably this the fact that thif patient's unpsually high rate of anomalies before this treatment was attributable to the previoug radiaticn 2ffect, which had occurred six years and more before. This incidence far suppassed the 4.5% nonmodal chromosome counts observed in normals in this laboratory. }Furthermore, the structural anomalies observed in this patient are extremely rare in contfol bilocds. Fortunately, the usual numerous sticiies performed under this contract hid been zarried out on this patient when we had given previous treatment doses. It Bad been observed then that very significant suppression of circulating lymphocytes had cccurred with each of the previous treatment doses 6 years and more before. Repeated|chramatograms ind other bicchemical studies of the blood following these earlier treatmentIdoses showed 1 marked rise in mono- and diicdotyrosine anda decline in the butanol extrdctable radioactivity in the circulation. These are all features which we had come fo believe ere evidences of radiation effect. The value of very long term detailed stikdy idvantage of being "tooled up" for such studies when the opportunity arises Yas iustrated in this case. The fact that a considerable population of cells with abnormal numbers ¢@f and the well chromosomes ilpparently persisted in this patient for at least 6 years. as shown in the b]bod drawn efore the present dose of 1512 was given,seems important. If cell lines stamming frem somatic cells which bear such anomalies can remain viable, the same might be ftrue of similarly affected reproductive cells in the gonads. If such a large mmber[of chromsaml thanges are demonstrable in tissues such as blood which does not specifically concentrate 31y, then significant alterations in other similar nonthyroidal celis such ds the eproductive cells should be considered even with much smaller doses of 13iz] it is ossible that the less devastating doses of 1311 may be more important becauge smaller oses may not be lethal although,perhaps more serious from the standpoint of Hamage to he cells. The total dosage of 151; given this patient was far greater than [that commonly sed in the therapy of Graves' disease. In view of the above observations it seemed appropriate that similar observations hould be made on patients who were receiving modest doses of 1311 for hypert .e. 5 to 15 millicuries rather than 167 as in the above described patient. coidisn, Pavid ' atcher, a Ph.D. student with Dr. Macintyre, continued this project to dete e whether here is a significant increase in anomalies in patients we selected for treafiment of raves' disease with 1211. om patients selected were studied in great detail, as