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Chemical form-dependent induction of hepatic zinc-thionein by arsenic administration and effect of co-administered selenium in mice.

Four arsenic compounds (m-arsenite, arsenate, methylarsonate (MMA), and dimethylarsinate (DMA) were administered to mice, either orally or by intraperitoneal injection, and the amounts of induced hepatic zinc-thionein (Zn-Th) were determined to investigate the chemical form dependency in metallothionein induction by arsenic. Several mice died within 24 h following intraperitoneal injection. The toxicity estimated from the lethality was in the order of m-arsenite greater than arsenate much greater than DMA approximately equal to MMA. Although all 4 arsenic compounds more or less induced Zn-Th following intraperitoneal injection, the dose of inorganic arsenic compounds observed to cause induction was one order lower than that of organic arsenic compounds. The induction of hepatic Zn-Th was also observed following oral administration, and inorganic arsenic compounds were again found to be more effective inducers via this route. To study the interactions of m-arsenite and selenite with regard to the amounts of Zn-Th induced, the two compounds were co-administered intraperitoneally. The amount of hepatic Zn-Th induced by the co-administration was one-fifth of that observed after selenite administration, and was almost the same as that after m-arsenite injection. Namely, when co-administered m-arsenite had the effect of lowering the level of Zn-Th induced following selenite administration, but the converse phenomenon was not observed.