Influence of hormono- and/or chemotherapy on the MXT mouse mammary tumor as monitored by 31P MRS.

We describe the early in vivo modifications that occurred in the MXT mouse hormone sensitive mammary tumor following various treatments which were monitored by 31P NMR spectroscopy. The MXT mouse mammary tumor was subjected to clinically relevant low-dose chemotherapy, i.e. seven cycles of 20 mg/kg cyclophosphamide (CPA) with or without an attempt at estrogenic cell recruitment prior to the CPA treatment. NMR measurements were begun at the end of the CPA treatment in order to evaluate the remaining 'long-term' chemotherapy-induced modifications within the MXT tumors. Statistical analyses performed on the 31P NMR parameters revealed that treatment had induced significant effects on bATP/PCr, Pi/PCr and PME/PDE only, with PCr being the most discriminating index. Its presence within MXT tumors was verified by means of an analysis of perchloric extracts. The results indicate a relative decrease of PME/PDE and a better conservation of PCr within the CPA-treated group as compared to the control one. This feature appeared even prior to any macroscopic modifications, as was the case within the group which contained tumors smaller than 120 mm2, and where no significant differences appeared between the mean sizes of the MXT cancers. In contrast, within the G2 group, which contained tumors equal to or larger than 120 mm2, CPA significantly slowed down tumor growth, while the administration of estradiol (E2) prior to CPA treatment antagonized the positive CPA-induced therapeutic effect. In conclusion, the non-invasive follow-up of the chemotherapeutic treatment of a clinically relevant mammary tumor model by 31P NMR spectroscopy backed up by statistical analyses revealed metabolic changes that appeared well before any modifications in histopathology or growth.