Thiol depletion and chemosensitization on nimustine hydrochloride by methionine-depleting total parenteral nutrition

Abstract

As an adjunct to cancer chemotherapy, we had succeeded in creating the methionine depletion in vivo, using the technique of total parenteral nutrition (TPN) by infusing an amino acid solution devoid of methionine and cysteine, as sole nitrogen source (Met-deplet. TPN). In Experiment 1, we demonstrated that the marked depletion of thiol was induced both in the liver and tumor tissues by Met-deplet. TPN in Sato lung carcinoma (SLC)-bearing rats. Then in Experiment 2, we also confirmed the presence of the enhancing effect on nimustine hydrochloride (ACNU) in Met-deplet. TPN to SLC. The tumor proliferation was inhibited significantly by Met-deplet. TPN even in conjunction with a small dose of ACNU, which showed no anti-tumor effect on the rats treated with methionine-containing amino acid solution, without apparent increase of the side effects in comparison with those in the control groups. On the other hand, to determine the carcinostatic effect on tumor-bearing animals, not only the size of the tumor but also its components, especially the percentage of necrotic tumor tissue (necrotic index), were considered to be important.