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The genotoxic effect of tryptophol


Tryptophol is a highly lipophilic compound which induces sleep in humans. In addition, it 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.

A pilot study, performed by scientists from several institutes and research associations in Croatia, evaluated the genotoxicity of tryptophol in vitro using four permanent cell lines of animal and human origin: ovary cells, alveolar epithelium, liver cells and blood monocytes (CHO, A549, HepG2 and THP-1 respectively). These particular cells were chosen as it was believed that they may be targets for the tryptophol compound. The tryptophol used in the study was purchased from a chemical company, rather than produced by the fungus, and was dissolved in DMSO before treatment to the four cell lines.

Immediately following tryptophol treatment, the alkaline comet assay was performed on all of four cell lines. A fluorescence microscope was coupled to a computer-based comet assay image analysis system (supplied by Perceptive Instruments Ltd.) Here, the comet parameters evaluated were tail length, tail intensity (percentage of DNA in the comet tail) and tail moment.

The results suggested that tryptophol applied in vitro for 24 hours damaged the DNA in HepG2, A549 and THP-1 cells, which was thought to be caused by bioactivation and/or decomposition of tryptophol. The tryptophol decomposition resulted in the formation of more genotoxic compound(s) and production of reactive species that additionally damaged the DNA. In comparison, lower levels of primary DNA damage were recorded in CHO cells, which lack metabolic activity. The researchers recommend that 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.

 

This case study is based on:
ASSESSMENT OF TRYPTOPHOL GENOTOXICITY IN FOUR CELL LINES IN VITRO: A PILOT STUDY WITH ALKALINE COMET ASSAY

Ivan Kosale, Snježana Ramic, Dubravko Jelic, Roberto Antolovic, Stjepan Pepeljnjak, and Nevenka Kopjar
Arh Hig Rada Toksikol 2011;62:41-49

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