Evaluation of the cell death pathway and apoptosis-stunning effect relationship after low- and high-dose I-131 administrations in rat thyroid tissue
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Objectives: This study had two aims; (1) to describe the cell death pathway (apoptosis or necrosis) induced by a low and high dose of radioiodine (I-131) in rat thyroid tissue in in vivo conditions and (2) to determine the role of apoptosis in the development of "stunning effect" in the thyroid tissue with low and high doses of I-131 application. Design: The experimental group consisted of 18 rats; low and high I-131 doses with a 1-week interval were administered to this group. At first, low doses were injected intraperitoneally (i.p.) (net injected dose was 51.54 +/- 8.6 mu Ci). After 1 week of the low-dose injection, high doses were also injected (net injected dose was 934.9 +/- 211.8 mu Ci). Thyroidal I-131 uptakes for both low- and high-dose applications were calculated by using a gamma camera after 24 hours of injections. Immediately after the uptake calculation, thyroid tissues were resected. A control group of 10 rats was also included in the study; in this group, I-131 was not administered. Thyroid tissues of this group rats were also resected. DNA was extracted from thyroid tissues, and damage was examined with the "DNA ladder by agaroz gel electrophoresis." Results: Thyroidal I-131 uptakes were calculated as 11.3% +/- 3.6% and 9.8% +/- 5.3% at the 24th hour after low- and high-dose I-131 applications, respectively. When the low- and high-dose uptake values were compared for each rat; a significant relationship was not found between thyroidal uptakes and injected low and high doses of I-131. When the chromosome images were examined, there was healthy DNA appearance in I rat; in 4 rats, only necrotic hyperfragmentations were observed; in 9 rats, both apoptotic specific fragmentations and necrotic hyperfragmentations were observed; and in 4 rats, apoptosis, necrosis, and healthy DNA appearances were seen together. In none of the rats, specific fragmentations concordant only with apoptosis was found. When the thyroidal uptake alterations were taken into consideration, significant difference was not found between first and second uptake calculations (p = 0.28). No significant relationship was also observed between thyroidal uptake alterations and apoptosis-necrosis-healthy DNA findings. Additionally, when we take into consideration the DNA results of only 13 of the rats that had reduced thyroidal uptake, a significant relationship could also not be observed between reduced uptake and apoptotic, necrotic, or healthy tissue findings. Interestingly, apoptotic and necrotic tissue or only necrotic, tissue findings were observed in the other 5 rats which had increased thyroidal uptake. Conclusions: Following I-131 administration, two types of cell death-both apoptosis and necrosis findings-have been observed in most of the rats. We think that the decreased uptake values are because of the probable stunning effect in thyroid tissue. We also investigated whether the stunning effect is related to apoptosis. According to our results, it can be concluded that the stunning effect is not related to tissue damage, cell decrease, or cell death. Alternatively, we think that this can be related to a radiation-induced reduction of iodine uptake/metabolism or a modified iodine transport mechanism. For further in vivo studies, this experimental model using normal rat thyroid tissue may be useful in investigating the cell death pathways induced by I-131 and its probable roles in the development of the stunning phenomenon.