Increased Radiation Tolerance of Mouse Tongue Epithelium after Local Conditioning

Abstract

The effect of local stimulation on mitotic activity and radiation tolerance was studied in mouse tongue mucosa. Silver nitrate solution (0·5–20%) was used for local conditioning. The most effective protocol comprised three daily treatments (days 0–2), yielding a delayed increase in 24 h mitotic counts by about 30% on days 5–7. The stimulating effect was independent of silver nitrate concentration. Sham treatment with saline or anaesthesia alone clearly depressed mitotic activity on days 2–4 without any subsequent overshoot. Radiation treatment was initiated on day 5 after three daily treatments with 3% silver nitrate solution. A top-up technique was employed, consisting of fractionated irradiation (300 kV X-rays) of the whole snout, followed by graded local test doses (25 kV X-rays) to induce denudation in a confined area of the inferior tongue surface. Silver nitrate conditioning did not alter the radiosensitivity of the epithelium to single local doses, but shortened the latency to denudation from 11 to 8 days. In contrast, a clear increase in tolerance to fractionated irradiation, delivering 5 × 2·5, 5 × 3·5, 5 × 4·5 Gy or 3 × 5·2 Gy in 7 days, was observed, equivalent to about four, two, one and two extra dose fractions. This approach may be a suitable way to increase radiation tolerance of oral mucosa in clinical radiotherapy.