<abstract xml:lang="en" xmlns="http://www.w3.org/1999/xhtml"><p>Tryptophol is an aromatic alcohol and secondary metabolite of the opportunistic fungus <italic>Candida albicans</italic>. Although its toxicity profile at cell level has been poorly investigated, recent data point to cytotoxic, cytostatic, and genotoxic effects in lymphocytes and the induction of apoptosis in leukaemic blood monocytes. In this pilot study we evaluated the genotoxicity of tryptophol <italic>in vitro</italic> on four permanent cell lines of animal and human origin: ovary cells, alveolar epithelium, liver cells, and blood monocytes using the alkaline comet assay. We selected cells that might be principal targets of tryptophol and other low-molecular geno(toxins) secreted by <italic>Candida albicans</italic> during host invasion. Our results suggest that tryptophol applied <italic>in vitro</italic> at 2 mmol L<sup>-1</sup> for 24 h damages DNA in HepG2, A549 and THP-1 cells, obviously due to bioactivation and/or decomposition of the parent compound, which results in the formation of more genotoxic compound(s) and production of reactive species that additionally damage DNA. On the other hand, notably lower levels of primary DNA damage were recorded in CHO cells, which lack metabolic activity. Future studies with tryptophol should look further into mechanisms involved in its toxic action and should focus on other cell types prone to infection with <italic>Candida</italic> spp. such as vaginal epithelial cells or keratinocytes of human origin.</p></abstract>

Tryptophol is an aromatic alcohol and secondary metabolite of the opportunistic fungus Candida albicans. Although its toxicity profile at cell level has been poorly investigated, recent data point to cytotoxic, cytostatic, and genotoxic effects in lymphocytes and the induction of apoptosis in leukaemic blood monocytes. In this pilot study we evaluated the genotoxicity of tryptophol in vitro on four permanent cell lines of animal and human origin: ovary cells, alveolar epithelium, liver cells, and blood monocytes using the alkaline comet assay. We selected cells that might be principal targets of tryptophol and other low-molecular geno(toxins) secreted by Candida albicans during host invasion. Our results suggest that tryptophol applied in vitro at 2 mmol L-1 for 24 h damages DNA in HepG2, A549 and THP-1 cells, obviously due to bioactivation and/or decomposition of the parent compound, which results in the formation of more genotoxic compound(s) and production of reactive species that additionally damage DNA. On the other hand, notably lower levels of primary DNA damage were recorded in CHO cells, which lack metabolic activity. Future studies with tryptophol should look further into mechanisms involved in its toxic action and should focus on other cell types prone to infection with Candida spp. such as vaginal epithelial cells or keratinocytes of human origin.

Assessment of Tryptophol Genotoxicity in Four Cell Lines <italic>In Vitro</italic>: A Pilot Study with Alkaline Comet Assay

Department of Microbiology, Faculty of Pharmacy and Biochemistry, University of Zagreb, Zagreb, Croatia

University Hospital for Tumours, Zagreb, Croatia

GlaxoSmithKline Research Centre Ltd., Zagreb, Croatia

School of Medicine, University of Rijeka, Rijeka, Croatia

Institute for Medical Research and Occupational Health, Zagreb, Croatia

Archives of Industrial Hygiene and Toxicology

Assessment of Tryptophol Genotoxicity in Four Cell Lines : A Pilot Study with Alkaline Comet Assay

Tryptophol is an aromatic alcohol and secondary metabolite of the opportunistic fungus Candida albicans. Although its toxicity profile at cell level has been...

Assessment of Tryptophol Genotoxicity in Four Cell Lines In Vitro: A Pilot Study with Alkaline Comet Assay

Publié en ligne: 21 mars 2011

Pages: 41 - 49

DOI: https://doi.org/10.2478/10004-1254-62-2011-2090

Mots clés
Candida albicans,

This content is open access.