31P NMR study of cisplatin‐ and doxorubicininduced changes in tumour metabolism in rats with a cisplatin‐sensitive or ‐resistant immunocytoma

摘要

AbstractThe response of tumours to treatment with the cytostatic drugs cisplatin (CDDP) or doxorubicin (DXR) was followedin vivoby31P NMR spectroscopy. A CDDP‐sensitive parent line (IgM‐I) and a CDDP‐resistant subline (IgM/CDDP) of the IgM‐immunocytoma grown s.c. on LOU/M WsL rats were used. Animals from both tumour groups (n= 33) were divided into 3 subgroups: CDDP‐treated (1 mg/kg), DXR‐treated (10 mg/kg) and control. In 3 out of the 4 treated subgroups where the tumours regressed to less than one half of the initial size,31P NMR spectroscopy revealed alkaline shifts of 0.31–0.41 pH units at day 4, while the ratio of nucleoside triphosphate to Piin the tumours, increased continuously to 250–435. Following CDDP treatment, the31P NMR spectra of the non‐responding IgM/CDDP tumours showed a similar pH increase (0.37 units). The ratio of NTP/Pishowed a temporary decrease to 63 ± 14 SEM at day 1, which was followed by a recovery to 130 ± 12 at day 2 and 119 ± 15 at day 4. The control tumours showed no change in pH and a gradual decrease in the ratio of NTP/Pi. In DXR‐treated rats the concentrations of DXR in the immunocytoma tumour and its subline were similar, but in the CDDP‐treated rats the IgM‐I tumours contained significantly higher levels of platinum than the IgM/CDDP tumours, both measured at 3 and 4 days after administration. The continuous increase in NTP/Piratio observed in the responding tumours, is a phenomenon characteristic of tumour regression, while the early temporary decrease in tumour NTP/Piratio could be associated with resistance to CDDP. Whether the reported response‐specific spectral change applies to other tumour types and other treatment regime