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Archives of Industrial Hygiene and Toxicology

The Journal of Institute for Medical Research and Occupational Health

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

Ivan Kosalec1 / Snježana Ramić1 / Dubravko Jelić1 / Roberto Antolović1 / Stjepan Pepeljnjak1 / Nevenka Kopjar1

Department of Microbiology, Faculty of Pharmacy and Biochemistry, University of Zagreb, Zagreb, Croatia1

University Hospital for Tumours, Zagreb, Croatia2

GlaxoSmithKline Research Centre Ltd., Zagreb, Croatia3

School of Medicine, University of Rijeka, Rijeka, Croatia4

Institute for Medical Research and Occupational Health, Zagreb, Croatia5

This content is open access.

Citation Information: Archives of Industrial Hygiene and Toxicology. Volume 62, Issue 1, Pages 41–49, ISSN (Print) 0004-1254, DOI: 10.2478/10004-1254-62-2011-2090, March 2011

Publication History

Published Online:
2011-03-21

Assessment of Tryptophol Genotoxicity in Four Cell Lines In Vitro: 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 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.

Procjena genotoksičnosti triptofola na različitim staničnim linijama u uvjetima in vitro: preliminarna istraživanja primjenom komet-testa u alkalnim uvjetima

Triptofol je aromatski alkohol i sekundarni metabolit oportunističkog mikroorganizma Candida albicans. Premda je njegova toksičnost na razini stanice vrlo slabo istražena, noviji podaci upućuju na citotoksične, citostatske i genotoksične učinke triptofola na ljudskim limfocitima te njegovu sposotnost izazivanja apoptoze u leukemijskim monocitima. Cilj ovog preliminarnog istraživanja bio je primjenom komet-testa procijeniti genotoksičnost triptofola u uvjetima in vitro na četiri vrste trajnih staničnih linija životinjskog i ljudskog podrijetla: stanicama jajnika, alveolarnom epitelu, stanicama jetre i monocitima. Izabrali smo one vrste stanica koje bi mogle biti potencijalne "mete" za djelovanje triptofola i srodnih mu niskomolekularnih geno(toksina) koje Candida albicans izlučuje tijekom infekcije domaćina. Dobiveni rezultati pokazuju da triptofol primijenjen u koncentraciji od 2 mmol L-1 tijekom 24 h u uvjetima in vitro izaziva oštećenja DNA u HepG2, A549 i THP-1-stanicama, vjerojatno zbog bioaktivacije i/ili razgradnje roditeljske molekule koje dovode do nastanka još genotoksičnijih spojeva i stvaranja reaktivnih radikala koji dodatno oštećuju DNA. Značajno niža razina oštećenja utvrđena je u CHO-stanicama koje nemaju enzime potrebne za metaboličku aktivaciju potencijalno genotoksičnih spojeva. Buduća bi istraživanja trebala bolje razjasniti mehanizme koji su u podlozi toksičnosti triptofola i usredotočiti se na druge vrste stanica osjetljive na infekciju mikroorganizmima iz roda Candida, primjerice vaginalne epitelne stanice ili keratinocite ljudskog podrijetla.

Keywords: aromatic alcohol; Candida albicans; DNA damage; permanent cell lines; secondary metabolite

Keywords: aromatski alkohol; Candida albicans; oštećenje DNA; sekundarni metaboliti; trajne stanične linije

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