Impact of preirradiation of the tumour bed on cell production rate and cell loss of human FaDu squamous cell carcinoma growing in nude mice

Purpose: To explore whether the tumour bed effect (TBE) in FaDu squamous cell carcinoma growing in nude mice is caused by a reduced tumour cell production rate and/or by increased tumour cell loss. Materials and methods: Human FaDu tumours were studied in NMRI nude mice. The volume doubling time (VDT) between 100 and 400 mm(3) was determined for tumours in unirradiated subcutaneous (sc) tissues (group 1), tumours in sc tissues preirradiated with 12.5 Gy (group 2), tumours irradiated in situ with 12.5 Gy (group 3), and tumours from group 3 re-transplanted into unirradiated sc tissues (group dr). Labelling index (LI), potential doubling time (T-pot), relative necrotic area and apoptotic index (AI) were evaluated in tumours from groups 1 and 2. Results: The median VDT were 2.6 days (95% CI 2-4) in group 1 and 7.0 days (4-15) in group 2 (P<0.001). The VDT were not significantly different between groups 2 and 3, and group 1 and 4. In groups 1 and 2, the T-pot values (3.1 +/- 0.6 days (SD) versus 2.9+/-0.5 days) and the LI were identical (10+/-1.5%). The median relative necrotic area was significantly larger in group 2 (37% [23-42]) compared with group (6% [0.3-27]). The apoptotic index was low (0.2%) and did not differ between groups 1 and 2. Conclusions: The results indicate that the TEE in FaDu squamous cell carcinoma is not caused by a reduced cell production rate in the viable tumour compartment. Rather, the TEE reflects a decreased viable tumour cell compartment due to increased cell loss. Necrosis appears to be the major component of the tumour bed induced cell loss in FaDu tumours, whereas apoptosis has no impact on the TEE in this model.