CYTOFLUOROMETRIC DNA ANALYSIS BY STATHMOKINETIC METHOD OF EXPERIMENTAL THYROID NEOPLASMS IN RATS

Thyroid neoplasms were induced in rats by the intraperitoneal injectio n of N-bis(2-hydroxy-propyl)nitrosamine as a carcinogenic substance an d by the oral administration of KClO4 as a promoter. The nuclear DNA c ontent was measured in tissue sections of the tumors by the stathmokin etic method with the use of vincristine, and was correlated with the h istopathological findings in the process of tumorigenesis and progress ion. Histological examination showed various types of lesions were pro duced in 47 surviving rats. A diploid pattern was seen in 82 (92%) of 89 tumors and an aneuploid pattern in 7 (8%) of 89 tumors. Papillary c arcinomas and mixed carcinomas only had a diploid pattern, while two o f 17 follicular carcinomas and five of 13 anaplastic carcinomas had an aneuploid pattern. On the other hand, benign proliferative nodules on ly had a diploid pattern. DNA heterogeneity was noted in seven maligna nt tumors. In four of them it was associated with the histopathologica l evidence of change, but in three there was no histological differenc e between the aneuploid and diploid areas other than a difference in t he mitotic index. Mitotic indices were significantly higher in the ane uploid than in the diploid areas. These findings suggest that changes in the DNA ploidy cause histological abnormalities and/or affect the m itotic index. It is hypothesized that a change occurs in some diploid cells in a region of a tumor, and that aneuploid cells develop from th e diploid cells which then acquire high proliferative activity.