Early cellular effects of Trp-P-1 on adult rat hepatocytes in primary culture.
Trp-P-1, a DL-tryptophan pyrolysis product, was previously known for its mutagenic and hepato-carcinogenic properties and for inducing nucleolar damage in adult rat hepatocytes in primary culture. In this paper, the effect of Trp-P-1 was investigated on DNA, RNA and protein synthesis in hepatocytes treated with 1, 5 and 10 micrograms/ml for 1, 2 and 4 h in order to determine the cascade of events which could occur in cells exposed to this agent. The inhibition of the 3 biosynthetic pathways was linearly dependent on the concentration of Trp-P-1 in the culture medium for each duration of treatment. For a given concentration, the degree of inhibition depended on the duration of incubation and varied according to the type of synthesis. DNA synthesis appeared as the most rapidly and strongly impaired: 16% of control values in hepatocytes treated with 10 micrograms/ml Trp-P-1 for 1 hour against 50.7% for RNA and 66.7% for protein synthesis. These data indicated that DNA should be the primary target of Trp-P-1 action in good agreement with the genotoxic activity of this agent. The complete recovery of RNA synthetic capability within 2 h after the removal of Trp-P-1 from the medium could however indicate that transcription was not definitely altered. By contrast the lack of protein synthesis recovery in a Trp-P-1 free medium for 24 h might signify the extended impairment of a step of translational process at the cytoplasmic level.
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Thybaud-Lambay
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M
Martin
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Decloitre
D000818:Animals; D002243:Carbolines / Q000494:pharmacology*; D002478:Cells, Cultured; D004261:DNA Replication / Q000187:drug effects; D007700:Kinetics; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D014176:Protein Biosynthesis / Q000187:drug effects; D012313:RNA / Q000096:biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains; D014158:Transcription, Genetic / Q000187:drug effects
D002243:Carbolines; D012313:RNA; D007770:L-Lactate Dehydrogenase; C019132:3-amino-1,4-dimethyl-5H-pyrido(4,3-b)indole