Glickson, 1989). Some previous studies revealed that administration of chemotherapy was often accompanied by reenergisation of the tumours, whilst in the case of certain regimens of chemotherapy and, especially, of hyperthermia, contrary effects were observed (for an overview see Steen, 1989). The PMEs as precursors of cell membrane phospholipid synthesis generally showed a decline following chemotherapy (Lutz et al., 1988;Daly et al., 1990). However, to our knowledge, only Evelhoch and coworkers (1987) investigated whether these changes are response-specific markers indicating significant tumour regression following chemotherapy or whether they are related to an unspecific action of chemotherapy, occurring independently of drug cytotoxicity. They studied the in vivo response of a mammary adenocarcinoma sensitive to adriamycin in comparison to a drug-resistant subline following treatment with adriamycin by 31P NMR spectroscopy. As they could not find any changes in the phosphorus metabolism in the resistant subline following chemotherapy, the 31P NMR spectroscopic effects observed in the sensitive subline were assigned as response-specific markers for chemotherapy. Moreover, Cohen et al. (1986) reported differences in the levels of phospholipids and PCr in a MCF-7 mammary carcinoma cell line resistant to adriamycin in comparison to the sensitive wild type. This result was confirmed in Evelhoch's study (1987) , 1984;Toohill et al., 1987).In the present study we investigated the phosphorus metabolism, by 31P NMR spectroscopy, in a xenografted human epidermoid carcinoma of the hypopharynx, growing subcutaneously in athymic mice, and in two sublines of the tumour with an increasing resistance to CDDP. In contrast to the above mentioned studies, the sublines exhibited only partial resistance to CDDP, which is closer to the situation observed in human patient tumours. By comparing three tumour lines with continuously decreasing sensitivity to CDDP, we expected to be able to assign the phenomena related to drug resistance regarding the initial levels of the phosphorus containing metabolites in the tumours and the alterations induced by CDDP with regard to the therapeutic efficacy. Parallel to NMR spectroscopy, tumour cytokinetics and histology were investigated in order to relate the changes observed in the 31P NMR spectra with generally accepted indicators of tumour response.
Materials and methodsTumour system and chemotherapy The investigations were performed on a moderately differentiated carcinoma of the hypopharynx which had been established from an untreated patient. The tumour was transplanted serially in male athymic mice (NMRI, nu/nu) and passaged by implanting tumour suspensions into the flank of the animals. From this tumour which was highly sensitive to cisplatin (CDDP), two sublines with an increasing degree of resistance to the drug were selected experimentally in vivo by repeated course treatment with CDDP over several generations. The subline with the lower resistance was maintained