Cell kinetic studies in the murine ventral tongue epithelium: mucositis induced by radiation and its protection by pretreatment with keratinocyte growth factor (KGF).

Abstract

Radiation kills or reduces reproductive capacity of proliferating cells, including stem cells. In the oral mucosae this can result in a decline in the number of cells in the tissue which, if severe enough, will result in the formation of an ulcer when the cellularity essentially reaches zero. We have used histometric measurements of cellularity following exposure to radiation in mouse ventral tongue epithelium as a model for oral mucositis (ulcer development). Here we provide further measurements of cellularity changes in the basal layer and in the epithelium as a whole at various times following 15, 20 or 25 Gy doses. The protective effects of prior treatment with keratinocyte growth factor (KGF) are also investigated. 20 Gy of 300 kV X-rays has become our standard reference dose and the changes in cellularity seen following this dose are highly reproducible, with minimum values being observed 6 days following irradiation. A higher dose results in a greater reduction of cellularity, although the minimum value also occurs at 6 days. A lower dose (15 Gy) results in a much shallower curve, with a minimum value being observed about 1 day earlier. These changes in cellularity can be related to the less sensitive index of mucositis, namely epithelial thickness. There is also a sharp peak in proliferation about 1 day after the minimum in cellularity, i.e. on day 7. The peak following a lower dose of radiation occurs a little earlier and, following the higher dose, the peak tends to be broader. Previous work and data presented in the preceding paper in this series has shown that KGF, given over a period of 3 days, results in a dramatic increase in epithelial thickness in oral mucosa, including the ventral tongue. As a result of the increased cellularity induced by KGF given before radiation, a delay in the fall in cellularity results, which is the consequence of the increased number of cells in the epithelium at the beginning of the study.