title: Assessment of tryptophol genotoxicity in four cell lines in vitro: a pilot study with alkaline comet assay.
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.
authors.affiliation: Department of Microbiology, Faculty of Pharmacy and Biochemistry, University of Zagreb, Croatia. ikosalec@pharma.hr
authors.forename: Ivan
authors.initials: I
authors.lastname: Kosalec
authors.forename: Snježana
authors.initials: S
authors.lastname: Ramić
authors.forename: Dubravko
authors.initials: D
authors.lastname: Jelić
authors.forename: Roberto
authors.initials: R
authors.lastname: Antolović
authors.forename: Stjepan
authors.initials: S
authors.lastname: Pepeljnjak
authors.forename: Nevenka
authors.initials: N
authors.lastname: Kopjar
mesh_terms: D000818:Animals; D002176:Candida albicans / Q000378:metabolism; D002460:Cell Line; D020552:Comet Assay; D004249:DNA Damage / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D007211:Indoles / Q000378:metabolism / Q000633:toxicity*; D009152:Mutagenicity Tests; D010865:Pilot Projects; D000438:Alcohols
chemical_list: D007211:Indoles; C005949:tryptophol; D000438:Alcohols