metallothionein and Leukemia-P388

The effect of metallothionein (MT)-I antisense oligodeoxynucleotide (ODN) on the growth of three kinds of tumor cells was studied, since MTs may be involved in cell growth. When MT-I antisense ODN was added to leukemia P388 cells, cell growth was inhibited in a manner dependent on the dose and incubation time. MT-I antisense ODN was also inhibitory for other tumor cell lines, i.e. Ehrlich carcinoma and sarcoma 180. A significant decrease in the level of MT, but not of Zn, was observed in MT-I antisense ODN-treated cells. On the other hand, control ODN did not inhibit the cell growth appreciably. These results indicate that MT-I expression may be necessary for the growth and survival of these tumor cells.

Topics: Animals; Cell Division; Leukemia P388; Metallothionein; Mice; Neoplasms, Experimental; Oligonucleotides, Antisense; Tumor Cells, Cultured; Zinc

The effect of preinduction of metallonthionein (MT) by bismuth subnitrate (BSN) on the adverse effects and antitumor activity of gamma-ray irradiation was investigated in mice. Preinduction of MT by oral administration of BSN significantly reduced the lethal effects and bone marrow injury caused by total body irradiation with gamma-rays. A significant increase in the MT concentration in bone marrow was observed in mice treated with BSN. In tumor-bearing mice, pretreatment with BSN did not compromise the antitumor activity of gamma-ray irradiation although bone marrow injury was remarkably suppressed. These results suggest that BSN pretreatment is an effective method for protection against side-effects in radiotherapy.

Topics: Adenocarcinoma; Animals; Bismuth; Bone Marrow; Colonic Neoplasms; Gamma Rays; Leukemia P388; Male; Metallothionein; Mice; Mice, Inbred Strains; Radiation Injuries, Experimental; Radiation, Ionizing

The participation of renal metallothionein (MT) in the toxicity and antitumor activity of cis-diamminedichloroplatinum(II) (cis-DDP) in male mice was examined. Preinduction of MT in the kidney by the s.c. administration of bismuth compounds decreased the lethality and renal and gastrointestinal toxicity caused by a single s.c. injection of cis-DDP. In the present study a correlation between the protective effect of pretreatment with bismuth nitrate against cis-DDP toxicity and the preinduced MT levels in the kidney was observed. Bismuth nitrate pretreatment showed no effect on the antitumor activity of cis-DDP against several transplantable tumors, probably because it induces MT in the kidney but not in tumor tissues. The fact that p.o. preadministration of bismuth subnitrate, an antidiarrheal drug, also depressed the lethal toxicity of cis-DDP is promising for its prompt application in medical attention. Thus, bismuth pretreatment allows higher doses of cis-DDP with no apparent toxicity, resulting in more efficient utilization of this anticancer drug.

Topics: Animals; Antacids; Bismuth; Cisplatin; Digestive System; Kidney; Leukemia P388; Male; Metallothionein; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL