engleski

Apoptosis and proliferation in X-irradiated submandibular gland

Radiation is an important treatment modality in the menagement of the head and neck cancer. Inadvertent damage to the salivary glands often results in a severe reduction of salivary flow, leading to irreversible and distressing oral complains by the treated patients. The complex relationship between apoptosis and cell proliferation is cardinal feature in maintenance normal arhitecture of the submandibular gland. Aim of our study was to examine apoptosis and proliferation in salivary gland during early (days 1, 3, 6, 10), and late (40 and 90 days) post-irradiation period and to assess their role in gland impairment caused by x- irradiation. Male C57BL/6 mice were locally irradiated in the region of the head and neck by a single dose of 7, 5 or 15 Gy. Control animals were sham-irradiated. Apoptosis was detected using TUNEL method and proliferation by immunohistochemistry for proliferation cell nuclear antigen (PCNA) in different gland compartments: acinar cells, intercalated duct and granular convoluted duct cells. Early period (1-10 days post irradiation) - apoptosis occurred rapidly, reaching a maximum 3 days post-irradiation. The percentage of apoptotic cells increased with the irradiation dose. At day 1 post-irradiation, cell proliferation was significantly reduced in comparison to sham-irradiated controls. After post-irradiation arrest of the cell cycle, proliferation increased, reaching a maximum at day 6. The proliferation response corresponded to the dose of irradiation. Late period - at 40 and 90 days post-irradiation gland cells of irradiated mice expressed higher apoptotic index than cells of unirradiated, control glands. At 40 days only in group irradiated with 7.5 Gy higher proliferation index was detected while at 90 days in both irradiated groups proliferation index was similar to control. We conclude that in early post-irradiation period apoptosis is followed by proliferation in the same rate, while in late post-irradiation period proliferation is not sufficient to sustain normal architecture of the gland.

apoptosis; proliferation; X-irradiation; salivary gland

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