Abstract
Tyramine, histamine and putrescine are the most commonly detected and most abundant biogenic amines (BA) in food. The consumption of food with high concentrations of these BA is discouraged by the main food safety agencies, but legal limits have only been set for histamine. The present work reports a transcriptomic investigation of the oncogenic potential of the above-mentioned BA, as assessed in the HT29 human intestinal epithelial cell line. Tyramine had a greater effect on the expression of genes involved in tumorigenesis than did histamine or putrescine. Since some of the genes that showed altered expression in tyramine-exposed cells are involved in DNA damage and repair, the effect of this BA on the expression of other genes involved in the DNA damage response was investigated. The results suggest that tyramine might be genotoxic for intestinal cells at concentrations easily found in BA-rich food. Moreover, a role in promoting intestinal cancer cannot be excluded.
Highlights
Biogenic amines (BA) are nitrogenous organic bases produced by practically all living organisms via the enzymatic decarboxylation and deamination of the corresponding amino acids1,2 - histamine from histidine, tyramine from tyrosine, etc
We recently showed that tyramine, histamine, putrescine and cadaverine are cytotoxic towards a human intestinal epithelial cell line at concentrations commonly reached in biogenic amines (BA)-rich food[16]
Using a human intestinal cell line, and a real-time quantitative PCR array covering 84 genes associated with different oncogenic pathways, the present work examines the possible oncogenic potential of tyramine, histamine and putrescine via the changes in the expression profile of genes involved in tumorigenesis
Summary
Biogenic amines (BA) are nitrogenous organic bases produced by practically all living organisms via the enzymatic decarboxylation and deamination of the corresponding amino acids1,2 - histamine from histidine, tyramine from tyrosine, etc. Tyramine and histamine showed a synergistic cytotoxic effect17 - a food safety concern given that these BA are commonly found together at high concentrations in certain BA-rich food (e.g., cheese)[5,6,9] This in vitro model allowed the modes of action of these BA to be assessed; tyramine, putrescine and cadaverine were shown to induce cellular necrosis, while histamine causes apoptosis[16] (del Rio et al, submitted). Using a human intestinal cell line, and a real-time quantitative PCR (qPCR) array covering 84 genes associated with different oncogenic pathways, the present work examines the possible oncogenic potential of tyramine, histamine and putrescine via the changes in the expression profile of genes involved in tumorigenesis. Since some of the genes showing a significantly different level of expression after tyramine exposure have been implicated in DNA damage-signalling and repair, the effect of this BA on the expression of genes involved in these processes was examined using a further real-time qPCR array
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