MNU-induced point mutation and activation of c-Ha-ras oncogene in cell lines derived from human pancreas explants.

Point mutation and activation of c-Ha-ras oncogene was studied at various stages of carcinogenesis in cell lines developed from MNU-treated human pancreas explants. DNAs from normal pancreas and nontumorigenic cell lines showed no transforming activity in NIH 3T3 cells whereas DNA from one of the tumorigenic cell lines transformed NIH 3T3 cells. In this cell line the point mutation was demonstrated to be at codon 12 of c-Ha-ras gene by the loss of an Msp I site. The mutation possibly affected the transcription of c-Ha-ras gene which in turn contributed to the transformation of these cells.