INCREASE IN HEPATIC METALLOTHIONEIN IN RATS TREATED WITH ALKYLATING-AGENTS

Male Sprague-Dawley rats were dosed (2 ml/kg, ip) with sodium iodoacetate (30 mg/kg), bromobenzene (1200 mg/kg), diethylmaleate (560 mg/kg), or iodomethane (46 mg/kg), 40 and 16 hr prior to being sacrificed and the concentration of hepatic metallothionein was determined. Treatment with the above agents resulted in a two- to fivefold increase in the concentration of hepatic metallothionein when compared to control rats fed ad libitum. In addition, treatment of rats with bromobenzene and sodium iodoacetate resulted in a two- to threefold increase in the concentration of hepatic metallothionein when compared to pair-fed control rats. Male rats were also dosed with either sodium iodoacetate (30 mg/kg, ip) or saline (ip) 40 and 16 hr prior to sacrifice and in each case with [35S]cystine 35 and 11 hr prior to sacrifice. Sodium iodoacetate treatment doubled the percentage of the 35S in the 100,000g supernatant incorporated into metallothionein. In addition, rats were treated with either sodium iodoacetate (30 mg/kg, ip) or sodium iodoacetate (30 mg/kg, ip) and after 3 hr cycloheximide (1.5 mg/kg, ip). Sodium iodoacetate treatment alone resulted in a significant increase in the concentration of hepatic metallothionein; however, in animals also treated with cycloheximide no increase was observed. These results indicate that the increase in hepatic metallothionein observed after treatment with sodium iodoacetate is due to an increase in the synthesis of metallothionein. © 1979.