SQUAMOUS-CELL CANCER CELL-LINES - SENSITIVITY TO BLEOMYCIN AND SUITABILITY FOR ANIMAL XENOGRAFT STUDIES

Bleomycin (BLM) is a natural antibiotic, toxic to dividing cells (G(2) /M-phase), also proven effective in squamous cell carcinomas (SCC). We have clinically shown that a short-range beta-emitting radionuclide c ombined to bleomycin (In-111-BLMC) is a tumor-targeting agent in SCCs. With higher radionuclide activities it may be possible to develop a m ore effective agent, to be tested in animal studies. Using a 96-well c lonogenic assay we investigated three SCC cell lines, grown in our own laboratory. IC20, IC50 and IC90 values for BLM were determined. The U T-SCC-12A and UT-SCC-12B cells were originated from a primary tumor an d a metastasis of the same patient. UT-SCC-12A cells were also inocula ted subcutaneously into nude mice and the tumor growth was analysed. T he IC50 value for UT-SCC-19A cell line was 4.0 +/- 1.3 nM. UT-SCC-12A and UT-SCC-12B were both more resistant to BLM; IC50 values were 14.2 +/- 2.8 nM and 13.0 +/- 1.1 nM, respectively. Within 35 days the weigh t of nude mice increased 2.8 +/- 0.6g. At 25 and 35 days after tumor i noculations the tumor volumes were 111 +/- 51 mm(3) and 874 +/- 577 mm (3), respectively. The calculated doubling time was 3.86 +/- 0.76 days . SCC cell lines demonstrate different sensitivity to BLM. Our SCC tum or xenograft model showed a rapid growth proper for radiochemotherapeu tic studies using In-111-BLMC. The uptake of In-111-BLMC in vivo has b een directly proportional to proliferation activity, and the tumors wi th high binding capacity could be predicted from animal model dose cal culations.