Thyroid cell proliferation in rats and induction of tumors by X-rays.

There are very few proliferating cells in the thyroid gland of normal adult rats, as measured by the labeling and mitotic index. One-tenth % 4-methyl-2-thiouracil in drinking water induced an exponential increase of thyroid weight after a lag phase of 2 days; the increase continued for 8 days and was followed by a plateau phase. The following sequence of events was found for the number of dividing follicular and stroma cells as well as for DNA synthesis: no significant changes during the 1st 2 days, a sharp increase between the 2nd and 8th days, a decrease between the 8th and 14th days, and an almost constant flow until the 24th day. Three-hundred rads of X-rays given to a nonproliferating thyroid gland induced tumor growth in 25% of the animals 18 months after irradiation. The same dose of irradiation, applied to a proliferating thyroid gland, increased the tumor incidence to 30% when administered in the lag phase, to 75% when administered at the peak of the proliferating phase, and to 62.5% when administered at the plateau phase. Subsequent treatment of irradiated animals with 4-methyl-2-thiouracil enhanced the number and the size of the thyroid tumors and lead to the occurrence of more carcinomas than appeared in animals treated with X-rays only or 4-methyl-2-thiouracil only.