Cytofluorometric DNA analysis by stathmokinetic method of experimental thyroid neoplasms in rats.

Abstract

Thyroid neoplasms were induced in rats by the intraperitoneal injection of N-bis(2-hydroxy-propyl)nitrosamine as a carcinogenic substance and by the oral administration of KCIO4 as a promoter. The nuclear DNA content was measured in tissue sections of the tumors by the stathmokinetic method with the use of vincristine, and was correlated with the histopathological findings in the process of tumorigenesis and progression. Histological examination showed various types of lesions were produced 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 carcinomas and mixed carcinomas only had a diploid pattern, while two of 17 follicular carcinomas and five of 13 anaplastic carcinomas had an aneuploid pattern. On the other hand, benign proliferative nodules only had a diploid pattern. DNA heterogeneity was noted in seven malignant tumors. In four of them it was associated with the histopathological evidence of change, but in three there was no histological difference between the aneuploid and diploid areas other than a difference in the mitotic index. Mitotic indices were significantly higher in the aneuploid than in the diploid areas. These findings suggest that changes in the DNA ploidy cause histological abnormalities and/or affect the mitotic index. It is hypothesized that a change occurs in some diploid cells in a region of a tumor, and that aneuploid cells develop from the diploid cells which then acquire high proliferative activity.