Early cellular effects of Trp-P-1 on adult rat hepatocytes in primary culture

Abstract

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.