Chromosomal instability and cytotoxicity induced by ribavirin: comparative analysis in cell lines with different drug-metabolizing profiles.

Autor: Librelotto CS; a Programa de Pós-Graduação em Biologia Celular e Molecular Aplicada à Saúde, Universidade Luterana do Brasil (ULBRA) , Canoas , Brazil., Simon D; a Programa de Pós-Graduação em Biologia Celular e Molecular Aplicada à Saúde, Universidade Luterana do Brasil (ULBRA) , Canoas , Brazil., de Souza AP; a Programa de Pós-Graduação em Biologia Celular e Molecular Aplicada à Saúde, Universidade Luterana do Brasil (ULBRA) , Canoas , Brazil., Álvares-da-Silva MR; b Serviço de Gastroenterologia, Departamento de Medicina Interna , Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul (UFRGS) , Porto Alegre , Brazil., Dihl RR; a Programa de Pós-Graduação em Biologia Celular e Molecular Aplicada à Saúde, Universidade Luterana do Brasil (ULBRA) , Canoas , Brazil.
Jazyk: angličtina
Zdroj: Drug and chemical toxicology [Drug Chem Toxicol] 2019 Jul; Vol. 42 (4), pp. 343-348. Date of Electronic Publication: 2017 Dec 04.
DOI: 10.1080/01480545.2017.1405970
Abstrakt: Ribavirin is an important component of the treatment for hepatitis C virus (HCV) infection and, in combination with the new direct-acting antiviral (DAA) agents, comprises the major current therapeutic regimens. This study evaluated the cytotoxicity and chromosomal instability induced by ribavirin using the in vitro cytokinesis-block micronucleus cytome (CBMN-Cyt) assay in two cell lines with different expression levels of drug-metabolizing enzymes: human hepatocellular carcinoma cells (HepG2) and Chinese hamster ovary (CHO-K1) cells. HepG2 cells were treated with nine concentrations (from 15.3 μg/ml to 3.9 mg/ml) and CHO-K1 cells were exposed to eight concentrations (from 15.3 μg/ml to 1.9 mg/ml) of ribavirin for 24 h. Ribavirin inhibited cell proliferation in both cell lines, but at different concentrations: 3.9 mg/ml in HepG2 and 244.2 μg/ml in CHO-K1 cells. No significant differences were observed regarding aspects of cell death in HepG2 and CHO-K1 cells, reflecting the absence of cytotoxic effects associated to ribavirin. Ribavirin did not increase the frequency of nucleoplasmic bridges (NPBs) and nuclear bud (NBUD). However, when compared to the negative control, a significant increase in micronuclei (MNi) frequency was observed in both cell lines. However, chromosomal instability was induced by higher concentrations of ribavirin in HepG2 cells (from 61.1 to 976.8 μg/ml), compared with CHO-K1 cells (15.3 and 30.5 μg/ml). These results demonstrate the potential of ribavirin to promote chromosomal instability, and suggest that cells with different expressions of drug-metabolizing enzymes show different susceptibility to ribavirin effects.
Databáze: MEDLINE
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