Induction of ras Oncogene Mutations and Hepatocarcinogensis in Medaka (Oryzias latipes Exposed to Diethylnitrosamine

Carcinogenesis and mutation events occurring in the medaka fish model exposed to the genotoxic pollutant diethylnitrosamine (DEN) for 48 h in the laboratory were studied. Histological examinations at five and seven months post-exposure showed 11 of 17 fish developing hepatic neoplasms. Genomic DNA examination of the livers of exposed fish showed an association of ras oncogene mutations and DEN-induced tumor formation. All three fish with ras gene mutations had mutations at codon 12, and one fish had an additional mutation at codon 16. The medaka fish model is useful for in vivo detection of the carcinogenic potential of environmental pollutants, such as DEN, in aquatic systems.