In this experimental study, investigators explored p53 tumor suppressor gene mutation induced by low and high doses of iodine-131 sodium iodide (I-131) in salivary gland tissue in rats. Group 1 consisted of 10 rats; low and high 1-131 doses were applied at a 1-wk interval. First, low doses of I-131 were injected. (The net injected dose was 47.5 +/- 9.2 mu Ci.) After 1 wk, high doses of I-131 were also injected. (The net injected dose was 1007.2 +/- 53 mu Ci.) Group 2 consisted of 5 rats, and only a low 1-131 dose was applied. (The net injected dose was 52.7 +/- 5.5 mu Ci.) The Control Group consisted of 5 rats that did not receive I-131. Thyroidal I-131 uptakes were calculated for Groups 1 and 2 with the use of a gamma camera after 24 h of injections. Immediately after uptake was calculated, salivary glands were resected in all groups and DNA was extracted for genotyping. Genomic DNA of the p53 gene exon 5 was examined by polymerase chain reaction single-strand conformational polymorphism. In Group 1, thyroidal I-131 uptakes were calculated as 12.45% +/- 4.14% and 9.66% +/- 6.73% after low-dose and high-dose I-131 applications, respectively. In Group 2, thyroidal I-131 uptake was calculated as 13.12% +/- 3.04%. In Group 1, p53 gene abnormality was seen in the salivary gland of only 1 of the rats. Double- and single-strand gene profiles showed that both alleles of this rat have a mutated single-strand conformational polymorphism profile of point mutation in the p53 gene exon 5. This rat received the highest low dose and the second highest total dose of I-131; its thyroidal uptakes were the second highest. in the other rats in Group 1, and in Group 2 and the Control Group, p53 gene abnormalities were not observed. In Groups I and 2, a significant relationship could not be discerned between thyroidal uptake of I-131 and p53 gene mutation in the salivary gland. No significant relationship was observed between thyroidal uptake alterations and p53 gene mutations in salivary glands in Group 1. A point mutation in the p53 gene exon 5 that was seen in only 1 of the rats in Group 1 seems related to the high-dose application of I-131, although coincidental occurrences could not be excluded. We believe that this topic is open to additional in vivo studies.