Dimethylnitrosamine-induced inhibition of hepatic protein synthesis in vitro and the effect of pretreatment with cystamine or pregnenolone-16alpha-carbonitrile.
Hepatic protein synthesis was investigated using a postmitochondrial supernatant system derived from the livers of rats that were given injections of a single dose of dimethylnitrosamine (DMN), 30 mg/kg. The time course and extent of DMN-induced inhibition in vitro were identical to those reported for the incorporation of amino acids into liver proteins in vivo, maximum inhibition being about 70% at 5 hr. Addition of specific inhibitors of chain initiation (polyinosinic acid and aurin tricarboxylic acid) to the postmitochrondrial supernatant system from DMN-treated rats caused only a slight additional inhibition, indicating that DMN predominantly affects translation by a block of initiation. Treatment with cystamine prior to DMN administration completely abolished the depression of protein synthesis and reduced by more than 90% the methylation by [14C]DMN of purine bases in liver DNA. Pretreatment with pregnenolone-16alpha-carbonitrile stimulated protein synthesis in controls but had no preventive effect in DMN-treated rats and did not reduce the extent of DNA alkylation in vivo.
D000478:Alkylation; D000818:Animals; D001312:Aurintricarboxylic Acid / Q000494:pharmacology; D002474:Cell-Free System; D003538:Cystamine / Q000494:pharmacology*; D004247:DNA / Q000378:metabolism; D003864:Depression, Chemical; D004128:Dimethylnitrosamine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D005260:Female; D006147:Guanine / Q000378:metabolism; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism*; D009602:Nitrosamines / Q000494:pharmacology*; D011069:Poly I / Q000494:pharmacology; D011132:Polyribosomes / Q000378:metabolism; D011284:Pregnenolone / Q000494:pharmacology*; D014176:Protein Biosynthesis; D051381:Rats; D013997:Time Factors
D009602:Nitrosamines; D011069:Poly I; D001312:Aurintricarboxylic Acid; D006147:Guanine; D011284:Pregnenolone; D004247:DNA; D004128:Dimethylnitrosamine; D003538:Cystamine