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The reducing agent Dithiothreitol (DTT) increases expression of c-myc and c- fos protooncogenes in human cells

Fund for the Replacement of Animals in Medical Experiments
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  • Medicine
  • Pharmacology


The objective of the present study was to assess the possible tumour promoting activity of the food mutagen 2-hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]pyridine (N-OH-PhIP), by studying its influence on the expression of three genes considered to be of relevance in the tumour promotion step. The genes were two proto-oncogenes, c-fos and c-myc, and the tumour suppressor gene, p53. We observed that the expression of the c-fos and c-myc genes was induced when human bladder epithelial cells were treated with a standard solution of N-OH-PhIP and dithiothreitol (DTT), previously shown to be genotoxic. However, when cells were treated with DTT alone, the expression of c-fos and c-myc was also transiently induced. We therefore conclude that DTT, and not N-OH-PhIP, induced oncogene expression. Induction of both c-fos and c-mye expression by a reducing agent, DTT, which is frequently used in in vitro toxicology studies, is a novel observation that suggests the need for a cautious interpretation of such studies.

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