Mutagenicity and DNA-damaging Potential of Clenbuterol and Its Metabolite 4-amino-3,5-dichlorobenzoic Acid in Vitro

Food Chem Toxicol. 2015 Mar;77:82-92. doi: 10.1016/j.fct.2014.12.023. Epub 2015 Jan 13.

Abstract

The aim of this study was to evaluate in vitro toxicity of clenbuterol and its metabolite 4-amino-3,5-dichlorobenzoic acid. Cytotoxicity and pro-oxidative effect of both compounds were studied on human colon adenocarcinoma cell line SW 480. No significant cytotoxic effect of either compound was observed. Results of an Ames test on Salmonella typhimurium did not indicate mutagenic activity of clenbuterol on TA 98 and TA 100 strains, regardless of metabolic activation. Potential mutagenic effects of the highest clenbuterol concentration (2500 ng/ml) were observed on the TA 1535 strain. The obtained results of alkaline comet assay on isolated human lymphocytes suggested that both compounds induced an increase of primary DNA damage in a concentration-dependent manner. 4-ADBA was a slightly more potent inducer of primary DNA damage as compared to clenbuterol. Chromosomal aberration analysis showed that clenbuterol caused a statistically significant increase in the total number of aberrant cells only at the highest concentration tested (3% vs. 0.7% in the negative control). The results of this study might represent a solid frame for designing and planning future studies with both compounds, which should further clarify their mechanisms of action and genotoxic/cytogenetic effects relevant for human risk assessment.

Keywords: Cytotoxicity; Genotoxicity; In vitro testing; Mutagenicity; Pro-oxidative effect; ß(2)-adrenoreceptor agonist.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Chromosome Aberrations / drug effects
  • Clenbuterol / toxicity*
  • Comet Assay
  • DNA Damage / drug effects*
  • Dose-Response Relationship, Drug
  • Humans
  • Lymphocytes / drug effects
  • Mutagenicity Tests / methods*
  • Salmonella typhimurium / drug effects
  • Structure-Activity Relationship
  • para-Aminobenzoates / toxicity*

Substances

  • para-Aminobenzoates
  • 4-amino-3,5-dichlorobenzoic acid
  • Clenbuterol