31P NMR study of cisplatin- and doxorubicin-induced changes in tumour metabolism in rats with a cisplatin-sensitive or -resistant immunocytoma.
The response of tumours to treatment with the cytostatic drugs cisplatin (CDDP) or doxorubicin (DXR) was followed in vivo by 31P 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 Pi in the tumours, increased continuously to 250-435%. Following CDDP treatment, the 31P NMR spectra of the non-responding IgM/CDDP tumours showed a similar pH increase (0.37 units). The ratio of NTP/Pi showed 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/Pi ratio observed in the responding tumours, is a phenomenon characteristic of tumour regression, while the early temporary decrease in tumour NTP/Pi ratio could be associated with resistance to CDDP. Whether the reported response-specific spectral change applies to other tumour types and other treatment regimens remains to be established.
Sijens
P E
PE
University Hospital Utrecht, Netherlands.
van Echteld
C J
CJ
van Rijssel
R H
RH
Lagendijk
J J
JJ
Neijt
J P
JP
de Jong
W H
WH
van der Minnen
A C
AC
de Groot
G
G
Seijkens
D
D
D000818:Animals; D002945:Cisplatin / Q000378:metabolism / Q000627:therapeutic use*; D004317:Doxorubicin / Q000378:metabolism / Q000627:therapeutic use*; D004351:Drug Resistance; D005260:Female; D006863:Hydrogen-Ion Concentration; D008223:Lymphoma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D009336:Necrosis; D010710:Phosphates / Q000378:metabolism; D010725:Phosphocreatine / Q000378:metabolism; D010758:Phosphorus; D051381:Rats; D011919:Rats, Inbred Strains; D012265:Ribonucleotides / Q000378:metabolism
D010710:Phosphates; D012265:Ribonucleotides; D010725:Phosphocreatine; D010758:Phosphorus; D004317:Doxorubicin; D002945:Cisplatin