HAZARD ASSESSMENT OF ANTINEOPLASTIC DRUGS AND METABOLITES USING CYTOTOXICITY AND GENOTOXICITY ASSAYS

Antineoplastic drugs are among the most toxic pharmaceuticals. Their release into the aquatic ecosystems has been reported, giving rise to concerns about the adverse effects, including cytotoxicity and genotoxicity, that they may have on exposed organisms. In this study, we analyzed the cytotoxicity...

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Bibliographic Details
Published in:Mutation research. Genetic toxicology and environmental mutagenesis 2023-11, Vol.892, p.503704-503704, Article 503704
Main Authors: Klein, Mariana de Oliveira, Francisco, Luiza Flavia Veiga, Gomes, Izabela Natália Faria, Serrano, Sergio V., Reis, Rui M., Silveira, Henrique C.S.
Format: Article
Language:English
Subjects:
Antineoplastic drugs
cytotoxicity
genotoxicity
HepG2
metabolites
micronucleus
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Summary:Antineoplastic drugs are among the most toxic pharmaceuticals. Their release into the aquatic ecosystems has been reported, giving rise to concerns about the adverse effects, including cytotoxicity and genotoxicity, that they may have on exposed organisms. In this study, we analyzed the cytotoxicity and genotoxicity of 5-fluorouracil (5-FU) and its metabolite alpha-fluoro-beta-alanine (3-NH2-F); gemcitabine (GEM) and its metabolite 2'-deoxy-2',2'-difluorouridine (2-DOH-DiF); as well as cyclophosphamide (CP) on the HepG2 cell line. Drug concentrations were based on those previously observed in the effluent of a major cancer hospital in Brazil. The study found that GEM, 2-DOH-DiF and 5-FU resulted in reduced cell viability. No reduction in cell viability was observed for CP and 3-NH2-F. Genotoxic assessment revealed damage in the form of nucleoplasmic bridges for CP and 3-NH2-F. The tested concentrations of all compounds resulted in significantly increased MNi and NBUDs. The results showed that these compounds induced cytotoxic and genotoxic effects in HepG2 cells at concentrations found in the environment. To the best of our knowledge, this study is the first to report on the cytogenotoxic impacts of the metabolites 3-NH2-F and 2-DOH-DiF in HepG2 cells. These findings may help in the development of public policies that could minimize potential environmental contamination. [Display omitted] •GEM, 2-DOH-DiF and 5-FU reduced cell viability of HepG2•CP and 3-NH2-F increased the number of nucleoplasmic bridges in cells•MNi and NBUDs were significantly increased at all concentrations and compounds tested•Cytogenotoxicity of 3-NH2-F and 2-DOH-DiF was described for the first time in HepG2
ISSN:1383-5718
1879-3592
DOI:10.1016/j.mrgentox.2023.503704