Radiation-induced changes in cellularity and proliferation in human oral mucosa.
OBJECTIVE
To quantify the oral mucosal cell density and proliferation rate during conventional radiotherapy of head-and-neck tumors and to compare these parameters with clinical scoring of oral mucositis.


METHODS
Between 1996 and 1999, 22 patients were included in this study. Mucosal biopsies were taken before or during the radiotherapy course (5 x 2 Gy/wk). Biopsies were incubated in vitro with tritiated thymidine immediately after excision to label DNA-synthesizing cells.


RESULTS
Epithelial cell density followed a biphasic radiation response. A steep decrease to about 50% of the preirradiation value (1000 cells/mm epithelium) during Week 1 was followed by a more gradual loss to about 400 cells at the end of treatment. The initial phase was based on the depression of proliferation, with 5-10 labeled cells/mm at the end of Week 1 vs. 60 labeled cells/mm in controls. Subsequently, proliferation was partially restituted at 20 labeled cells/mm. A significant difference in cell numbers was seen between Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer Grade 0 (approximately 850 cell/mm) and Grade 2 (325/mm) or Grade 3 (370/mm). No significant differences were observed between reaction grades 1, 2, and 3.


CONCLUSIONS
Conventionally fractionated radiotherapy induces a rapid suppression in cell production in Week 1, which results in a prompt reduction in cell numbers. Subsequently, a partial restoration of proliferation significantly reduces the rate of cell loss. These processes clearly precede the clinical response. Regeneration, defined as restoration of cellularity, is already under way when the maximal clinical response is observed. Clinical reaction grading corresponds poorly to cellular density measures during conventional fractionation.
Dörr
Wolfgang
W
Klinik und Poliklinik für Strahlentherapie und Radioonkologie, Medizinische Fakultät Carl Gustav Carus der Technischen Universität, Dresden, Germany. doerr@rcs.urz.tu-dresden.de
Hamilton
Christopher S
CS
Boyd
Teresa
T
Reed
Barry
B
Denham
James W
JW
D002452:Cell Count; D002455:Cell Division / Q000528:radiation effects; D005260:Female; D006258:Head and Neck Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D008297:Male; D009061:Mouth Mucosa / Q000166:cytology / Q000528:radiation effects*; D011832:Radiation Injuries / Q000473:pathology*; D016196:S Phase; D013280:Stomatitis / Q000209:etiology / Q000473:pathology*