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. 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 stvara