Cell cycle perturbations in heterotransplanted squamous-cell carcinoma of the head and neck afterMitomycin C andCisplatin treatment

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Abstract
Cell kinetic studies are of interest for clarifying the concepts of chemotherapeutic strategy in the multimodality therapy of advanced squamous-cell carcinoma of the head and neck. A poorly-differentiated squamous-cell carcinoma of the head and neck heterotransplanted to nude mice was used for analyses of chemotherapeutically induced cell cycle perturbations. The heterotransplanted tumour, in its 15th or later passages in nude mice, was treated with either Mitomycin C or Cisplatin. After determination of dose-response relationships and toxicity, treated tumours were biopsied at different times and cell cycle distribution pattern, 3HTdR incorporation into DNA, histology and tumour volume were recorded. Mitmycin C and Cisplatin gave the same pattern of cell cycle perturbations, although the changes induced by Cisplatin were more profound. There was an initial increase of the fraction of cells in the S phase, concomitant with a reduction of the fraction of cells in G0+G1 phase. When these perturbations were normalized a transient increase of the fraction of cells in G2+M phase was observed. However, while Cisplatin caused an initial transient depression of DNA synthesis, the Mitomycin-C-treated tumours exhibited a short-lasting increase of DNA-synthesis. The maxima of the induced changes in cell cycle phase distribution and DNA-synthesis lasted for only 24–48 h, which may be of importance for scheduling combinations of drugs. Though both drugs induced profound changes in tumour volume growth and cell kinetics, there was no change in the histopathological picture of the treated tumours. Routine histopathological examination is thus not likely to be of value evaluating the effect of chemotherapy.