Abstract:
:Adult rat hepatocytes in primary culture were used to study the effect of tryptophan pyrolysis products on the transcriptional process. Hepatocytes were treated with 1, 5 and 10 micrograms/ml of 3-amino-1,4-dimethyl-5H-pyrido-[4,3-b]-indole (Trp-P-1) or 3-amino-1-methyl-5H-pyrido-[4,3-b]-indole (Trp-P-2) for 2 and 4 h. The ultrastructural study revealed the appearance of nucleolar microsegregation accompanied by a reduction in peri- and interchromatin fibrils and granules in hepatocytes exposed to 10 micrograms/ml of each pyrolysate for 1 or 2 h. Biochemical investigation showed that the incorporation of [3H]uridine into nuclear RNA of treated hepatocytes was strongly decreased. Time- and concentration-related inhibition have been established; however, the inhibitory effect of Trp-P-1 was always superior to that of Trp-P-2. The determination of Mg2+-dependent RNA polymerase activity in an in vitro system functioning with isolated rat liver nuclei incubated in the presence of Trp-P-1 or Trp-P-2 showed a 40% inhibition of this activity. After a 1-h exposure of hepatocytes to 5 and 10 micrograms/ml of Trp-P-1, the recovery of RNA synthesis capacity was complete by 2 h and that of normal ultrastructural aspect was achieved within 4 h. All these results indicated that Trp-P-1 and Try-P-2 acted at the nucleolar level by a blockade of pre-rRNA synthesis and at the extranucleolar by decreasing the ultrastructural RNP responsible for hnRNA synthesis.
journal_name
Carcinogenesisjournal_title
Carcinogenesisauthors
Thybaud-Lambay V,Decloitre F,Moulé Y,Florentin Ydoi
10.1093/carcin/4.4.481subject
Has Abstractpub_date
1983-01-01 00:00:00pages
481-8issue
4eissn
0143-3334issn
1460-2180journal_volume
4pub_type
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