Mouse tumours induced by DEN alone frequently harbour initiating activating mutations in either Hras or Braf proto-oncogenes.[12], [13] In a related model in which tumours are induced using DEN as an initiator followed by phenobarbital as a tumour promoter, chromosomal instability and activating mutations in β-catenin have been implicated in tumour progression.14 This evidence concerns the gene HRAS and neoplasm.