THE REDUCING AGENT DITHIOTHREITOL (DTT) INCREASES EXPRESSION OF C-MYCAND C-FOS PROTOONCOGENES IN HUMAN-CELLS

The objective of the present study was to assess the possible tumour p romoting activity of the food mutagen droxyamino-1-methyl-6-phenylimid azo[4,5-b]pyridine (N-OH-PhIP), by studying its influence on the expre ssion of three genes considered to be of relevance in the tumour promo tion step. The genes were two proto-oncogenes, c-fos and c-myc, and th e 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 trea ted with DTT alone, the expression of c-fos and c-myc was also transie ntly induced. We therefore conclude that DTT, and not N-OH-PhIP, induc ed oncogene expression. Induction of both c-fos and c-mye expression b y a reducing agent, DTT, which is frequently used in in vitro toxicolo gy studies, is a novel observation that suggests the need for a cautio us interpretation of such studies.