RELATIONSHIP BETWEEN THE PARAMETERS CELLULAR-DIFFERENTIATION, DOUBLING TIME AND PLATINUM ACCUMULATION AND CISPLATIN SENSITIVITY IN A PANEL OF HEAD AND NECK-CANCER CELL-LINES

Patients with head and neck squamous cell carcinoma (HNSCC) treated wi th cisplatin show a large inter-individual variation in tumor response . Little is known about factors that contribute to this variation. The aim of our study was to correlate the sensitivity to cisplatin with a number of cellular parameters using a panel of 10 human HNSCC cell li nes. A 7-fold variation in response after 72 hr of exposure to cisplat in as determined in a colorimetric proliferation assay was observed. T he IC50 values did not correlate with the DNA index, the cellular doub ling time or the expression of differentiation markers, Intracellular platinum (Pt) concentrations were measured by atomic absorption spectr oscopy after exposing the cells to 10 mu M cisplatin for 1-72 hr. The intracellular Pt levers increased up to 24 hr. One cell line, derived from the tumor of a patient previously treated with radiotherapy, accu mulated much more Pt than the other cell lines. For these other cell l ines, a significant positive correlation was found between Pt accumula tion and sensitivity. In conclusion, cisplatin-induced growth inhibiti on in HNSCC in vitro is generally positively correlated with cellular Pt levels. However, the fact that occasionally cancer cells can surviv e despite high intracellular Pt levels indicates that additional param eters are needed to explain a response unequivocally. (C) 1997 Wiley-L iss, Inc.