Effects of toluene on protein synthesis and the interaction with ethanol in hepatocytes isolated from fed and fasted rats.
The effects of three different concentrations (about 10, 100 and 1000 microM) of toluene on protein synthesis were studied in hepatocytes isolated from fed and fasted rats after 60 and 120 min. of incubation. The interaction between ethanol (60 mM) and the low and high toluene concentrations were also tested. To measure protein synthesis, 14C-valine was used as the precursor amino acid. Total valine concentration was 2 mM to ensure near-constant specific radioactivity of precursor. Toluene concentrations were measured by head-space gas chromatography. Protein synthesis was unchanged in the presence of low toluene concentrations. Intermediate toluene concentration decreased protein synthesis by about 20% and high toluene concentration decreased protein synthesis by about 60%. Protein synthesis was similar in cells from fed and fasted rats. Ethanol alone inhibited protein synthesis by 20-30%, more in fasted than in fed rats. Toluene and ethanol in combination inhibited protein synthesis additively. The high toluene concentration with or without ethanol appeared to inhibit synthesis/secretion of export proteins in hepatocytes from fasted rats. In conclusion, our study indicates that toluene in relatively high concentrations inhibits general protein synthesis in isolated rat hepatocytes. Toluene and ethanol seems to inhibit protein synthesis additively.
National Institute of Forensic Toxicology, Oslo, Norway.
A
A
Smith-Kielland
A
A
Ripel
G
G
Gadeholt
D000818:Animals; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology*; D005215:Fasting; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D014176:Protein Biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains; D014050:Toluene / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D014633:Valine / Q000378:metabolism
D014050:Toluene; D000431:Ethanol; D014633:Valine