metallothionein and Sarcoma-180

Based on the previous finding that hepatic metallothionein (MT) level was tumor-growth dependently elevated in tumor-transplanted mice, the mode of induction of hepatic MT in tumor-bearing mice was comparatively studied with inflammation-induced and stress-subjected mice. The prefeeding with zinc (Zn)-deficient diet for 1 wk suppressed both the growth of tumor and the increase of hepatic MT and Zn in tumor-bearing mice. The postfeeding with Zn-deficient diet also suppressed hepatic MT induction in the course of tumor growth. On the other hand, in the other two experimental model mice, the prefeeding with Zn-deficient diet did not suppress the increase of hepatic MT and Zn. Further, the dexamethasone treatment stimulated hepatic MT induction in tumor-bearing mice, but rather reduced that in inflammation-induced mice. These results suggest that hepatic MT was induced uniquely in tumor-bearing mice and that Zn may play a key role for the induction of hepatic MT by tumor transplantation.

Topics: Animals; Carcinoma, Ehrlich Tumor; Dexamethasone; Diet; Liver; Male; Metallothionein; Mice; Neoplasm Transplantation; Restraint, Physical; Sarcoma 180; Stress, Physiological; Turpentine; Zinc

The effects of Lisheng-Se (Seleninized wheat germ) on metallothionein (MT) induction, lethal systemic toxicity, nephrotoxicity, hemotoxicity and anticancer activity of cisplatin (CDDP), were investigated in mice. The systemic toxicity of CDDP was significantly reduced by preadministration of Lisheng-Se (P < 0.05 or P < 0.01). The protective effects were better than its inorganic form (Na2SeO3) and Bi (BSN), (0.05 < P < 0.1). The MT level in the liver, kidney, heart and tumor tissues of mice treated with one of those compounds was determined. The results show that the levels of MT induced by Lisheng-Se were significantly increased in liver and kidney (P < 0.01 and P < 0.05). It was just in conformity with the conclusion that the best protective effect appeared in the groups treated with Lisheng-Se. These results suggest that increased MT synthesis in the liver and kidney may be involved in the protective effects of Lisheng-Se tested on the lethal toxicity, nephrotoxicity and hemotoxicity produced by CDDP. The experiments also show that Lisheng-Se did not affect the anticancer activity of CDDP in vitro and in vivo, while the MT level was not increased in cancer (P < 0.05), so Lisheng-Se might not only improve the therapeutic index of CDDP, but also did not cause drug-resistance of cancer cells.

Topics: Animals; Cisplatin; Kidney; Lethal Dose 50; Leukemia L1210; Liver; Metallothionein; Mice; Organoselenium Compounds; Sarcoma 180; Sodium Selenite

The preventive effects of Zn Glycyrrhizate (Gly-Zn) on lethal toxicity, nephrotoxicity, hemotoxicity, testicular toxicity and anticancer activity of cisplatin (CDDP) were investigated in mice. The toxicity of CDDP evaluated by the above criterion was significantly reduced by preadministration of Gly-Zn 400 mg.kg-1.d-1 x 5 (P < 0.05 or P < 0.01). The protective effects were better than bismuth subnitrate (BSN) which has been studied previously (0.05 < P < 0.1). The metallothionein (MT) level in the liver, kidney, heart and cancer of mice treated with one of these compounds were determined. The results showed that the levels of MT induced by Gly-Zn were significantly increased in liver and kidney (P < 0.05). It was just in conformity with the conclusion that the best protective effect appeared in the groups treated with preadministration of Gly-Zn. These results suggest that increased MT synthesis in the liver and kidney may be involved in the protective effect of Gly-Zn on the toxicities produced by CDDP. The experiments also showed that Gly-Zn did not affect the anticancer effect of CDDP in vitro and in vivo, while the MT level was not increased in cancer (P < 0.05), so Gly-Zn might improve the therapeutic index of CDDP.

Topics: Animals; Antineoplastic Agents; Bismuth; Cisplatin; Drug Synergism; Female; Glycyrrhetinic Acid; Glycyrrhizic Acid; Lethal Dose 50; Male; Metallothionein; Mice; Neoplasm Transplantation; Sarcoma 180; Testis; Tumor Cells, Cultured

To investigate Zn and Cu accumulation and isometallothionein (iso-MT) induction in ascites-sarcoma S180A cells, 5 micrograms of Zn2+ or Cu2+/g body weight was administered to tumour-bearing mice intraperitoneally. In the tumour cells the Zn or Cu concentration increased more than in the host liver, which is the target organ for those metals; the maximum Zn or Cu level was about 2-3 times that in the host liver. The amounts of Zn-MT or Cu-MT accumulated in the tumour cells and host liver were proportional to such dose accumulation levels in the each cytosol; the maximum level of Zn-MT or Cu-MT was 4 or 2 times higher than in the host liver. MT accumulated in the tumour cells showed two subfractions (MT-1 and MT-2); the ratio of Zn (or Cu) bound to MT-1 to that bound to MT-2 in the host liver and tumour cells was 1.0 (or 1.0) and 0.7 (or 0.25) respectively, suggesting that the induction level of MT-2 in the tumour cells is more than that of MT-1. The h.p.l.c. profiles (using an anion-exchange column) of the isolated MT-1 and MT-2 subfractions from Zn-treated normal-mouse liver showed a single peak (MT-1-1) and two peaks (MT-2-1 and MT-2-2) respectively; mouse MTs were separated into three isoforms. In the ascites cells, the MT fraction obtained by a gel filtration was also separated into three isoforms; however, the amount of MT-2-1 isoform was 3 times that in the Zn-treated normal-mouse liver.

Topics: Amino Acids; Animals; Chromatography, High Pressure Liquid; Chromatography, Ion Exchange; Copper; Female; Liver; Metallothionein; Mice; Neoplasm Transplantation; Sarcoma 180; Zinc