Time- and dose-related changes in the expression of substance P in salivary glands in response to fractionated irradiation.

PURPOSE

The expression of different neuropeptides in the innervation of submandibular and parotid glands of the rats was examined 2 and 5 days after initiation of radiation treatment as well as 10 and 180 days following the termination of irradiation.

METHODS AND MATERIALS

The irradiation was given on 2 or 5 consecutive days with daily doses of 4-8 Gy up to a total dose of 20-40 Gy. Immunohistochemical methods were used for the demonstration of substance P (SP), calcitonin gene-related peptide (CGRP), neuropeptide Y (NPY) and, the rate-limiting enzyme in the catecholamine synthetic pathway, tyrosine hydroxylase (TH). The content of SP was also analyzed by the use of radioimmunoassay (RIA).

RESULTS

In the parenchyma of both the submandibular and the parotid glands of control animals as well as after 2 days of irradiation treatment, a few nerve fibers showing SP-like immunoreactivity (LI) were observed. A marked increase in the expression of SP in the innervation of the parenchyma in both glands was observed 10 days after cessation of radiation treatment. The number of stained nerve fibers and the intensity of fluorescence in the fibers seemed to be dose dependent because the group subjected to a total dose of 40 Gy displayed a more pronounced staining intensity than that treated with 30 Gy. These results were supported by the RIA analysis. One hundred eighty days after treatment no obvious differences in SP-expression were seen between control and irradiated animals. No acute and long-term alterations were seen with regard to the other peptides and TH.

CONCLUSIONS

These results suggest that specific dose- and time-dependent changes in the expression of SP in the parenchyma of both submandibular and parotid glands occur in response to fractionated irradiation. The observations add further aspects to the tissue differences in physiological response and sensitivity to irradiation.