metallothionein and Urogenital-Neoplasms

In this paper we demonstrate the relationship between the antitumor activity of cis-diamminedichloroplatinum (II) (CDDP) and inducibility of metallothionein (MT) and glutathione (GSH) of genitourinary tumors.. The chemosensitivity test was performed in athymic mice bearing tumors derived from the human tumor cell lines: ACHN (renal cell carcinoma), NMB-1 (urinary bladder transitional cell carcinoma), and NMT-1 (testicular embryonal cell carcinoma). A single dose of CDDP (25 mumol/kg body weight), was administered i.p. to athymic tumor bearing mice. Concentrations of platinum, MT, and GSH were measured in organ and tumor homogenates 24 h after CDDP administration.. We observed that tumors derived from NMB-1 and NMT-1 were very sensitive to CDDP, but ACHN derived tumors were resistant to CDDP. Measurement of platinum concentrations in tumor tissues revealed no correlation to the observed chemosensitivities of the tumors. Furthermore, 24 h after CDDP administration, the levels of MT and GSH in NMB-1 and NMT-1 derived tumors were lower them or equal to those of control mice. In contrast, mice bearing tumors derived from ACHN exhibited a 1.7-fold and a 2.1-fold increase in MT and GSH, respectively, as compared to control mice.. These findings suggest that the inducibility of MT and GSH in tumor tissues following CDDP administration may be a contributing factor in the development of CDDP resistance in renal cell carcinoma.

Topics: Animals; Cisplatin; Drug Resistance, Neoplasm; Glutathione; Humans; Kidney Neoplasms; Male; Metallothionein; Mice; Mice, Nude; Neoplasm Transplantation; Testicular Neoplasms; Tumor Cells, Cultured; Urinary Bladder Neoplasms; Urogenital Neoplasms