'ineth 8Oks 7000 to 5000 rads there was some impairment of mitotic activity shortly after I and some persistent impairment was demonstrable for the remainlier of the 2 eethe aninal In some animals some temporary impairment was seen below —L000 ls and in some of this group of animals subsequently the maximal enlargement] of the ind on chronic thiouracil could not be achieved. It must be recognized, howpver, that sacity for hypertrophy declines with age so that failure to recover earlier [impairment ‘not actually be attributable to radiation. Furthermore, the capacity to respond ‘th increased mitotic activity /1 radiated animals was more like a non-radiatkd animal a later age. With 9000 to 20,000 rads the recovery of mitotic activity at P6 days | 5 months was not complete. With 14,000 to 30,000 the capacity for mitotic] activity ; Only about 4s that of non-radiated animals. It was at about this dose level that y little significant increase in thyroid weight could be produced by thiourficil later life until the animal was developing a neoplasm. Among animais sacrificed ft 4 weeks re had been considerable temporary recovery in ability to respend to the stimulus n after doses as high as 14,000 to 30,000 in one series and 12,000 to 15,00) in the othex was at this level of rad dose that neoplasms were most likely to ultimately shout the added stimulus of thiouracil. appear When neoplasms were clearly formed, the incidence of mitotic labeling in f-he lesion 3 usaally much greater than that in,the extranodular tissue. Only in the more rently prepared autoradiograph for 1311 content was the iodine uptake rin of the splasm satisfactorily demonstrated. However, as far as observations go, it Bppears it those neoplasms with the most abundant labeling with tritiated thymidine fin nuclei $5 little 13112. I uptake. Figure 14 illustrates an autoradiograph of a solid cellular tumor wit! All types of histologic patterns of thyroid neoplasms have been found. pillary and follicular lesions have been the most-common thus far. Such a shown in Figure 15. ed Iksion These are usually found where chronic thiouracil has heen super- sosed on radiation. It has been discovered that most of the lesions found ifn animals at are radiated but not given thiouracil are solid cellular lesions and mst] appear Lte undifferentiated. One such neoplasm is seen in Figure 16. This animal fFeceived pe of 1317 delivering 5126 rads. No thiouracil was given other than the brfief few days stimulate acute mitotic activity. The animal was sacrificed at 18 months. The toradiograph shows an enormous concentration of nuclei bearing the tritiated thymidine sel at a point where the very undifferentiated neoplasm is breaking through [the capsule. > cells that are labeled only had an opportunity to collect thymidine for ar hour and 2y only collected _it when preparing to divide. Therefore, the encrmous numitr of cells selec speaks forarate at which these cells are miltiplying at the point of Hreak through. By making routine tritiated thymidine autoradiographs it has been hoped that we nt learn at what time neoplasms begin to develop following I and therefdre find am at or near their inception. It has been assumed that any cluster of cellB destined be a neoplasm will display a different rate of incorporation of tritiated tfhymidine its nuclei than will cells of the surrounding tissue as shown in Figure 16 [and 17. After 12 to 15 months radiated thyroids show some areas of variability follicle size and cell size. respect At this time the labeling of mclei is not always > iformly displayed. Figure 18. Although there may be no discretely encapsulated groups celis which are clearly a neoplasm, the tendency for cell division seems mre avalent in some areas than in others. The non-uniform distribution of labelling with © itiated thymidine presumably relates to the nodularity that evolves when theake glands 2 stimlated to hypertrophy. It appears that ultimately such glands will bq found to nmtain lesions whose histologic appearance, degree of encapsulation and discretely |