Journal article
Effect of inhibitors of microsomal enzymes on aflatoxin B1-induced cytotoxicity and inhibition of RNA synthesis in isolated rat hepatocytes
Biochemical and biophysical research communications, v 115(1), pp 15-21
30 Aug 1983
PMID: 6412712
Abstract
Previous studies conducted in this laboratory demonstrated that AFB1 activation and deactivation was effectively inhibited by metyrapone and TCPO in isolated hepatocytes. The present study was undertaken to study the toxic effect of AFB1 on hepatocyte and RNA synthesis, and to assess the influence of the inhibitors on AFB1-induced cytotoxicity and AFB1-inhibited RNA synthesis. AFB1 at 50 μM was toxic and inhibited macromolecular synthesis by greater than 70% at 180 min of incubation whereas at lower concentrations of AFB1 (0.05–10 μM) dose-and time-dependent decreases in cell viability, protein and RNA synthesis were observed. Using [3H]-AFB1 (0–1.5 μM), the uptake and covalent binding of the toxin were also dose-and time-dependent. Initial rates of these processes to reach half-maximum was found to be 0.25 μM AFB1. In cells treated with AFB1 (5 μM) and metyrapone (1.0 mM) or SKF-525A (10 μM), the cell viability was similar to the control and [3H]-uridine incorporation was significantly higher than AFB1 treated cells. AFB1 and TCPO (0.5 mM) treated cells exhibited further decreases in cell viability and RNA synthesis. Results suggest that the binding of AFB1 to DNA and impairment of transcriptional activity may lead to cell death.
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Details
- Title
- Effect of inhibitors of microsomal enzymes on aflatoxin B1-induced cytotoxicity and inhibition of RNA synthesis in isolated rat hepatocytes
- Creators
- John J. Ch'ih - Hahnemann University HospitalTzu Lin - Hahnemann University HospitalThomas M. Devlin - Hahnemann University Hospital
- Publication Details
- Biochemical and biophysical research communications, v 115(1), pp 15-21
- Publisher
- Elsevier
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biochemistry and Molecular Biology
- Web of Science ID
- WOS:A1983RF54000003
- Scopus ID
- 2-s2.0-0020558691
- Other Identifier
- 991019184063304721
InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Web of Science research areas
- Biochemistry & Molecular Biology
- Biophysics