A mouse model system was established for the rapid induction of tumors in tissues that are also being transformed by raf or raf/myc oncogene carrying retroviruses. Tumor induction involved transplacental inoculation of mice at day 16 of pregnancy with ethylnitrosourea (ENU) followed by promotion with butylated hydroxytoluene (BHT). Ninety percent of the animals treated with initiator (ENU) and promoter (BHT) developed tumors within 5 to 14 weeks. In the absence of promotion, 40% of the animals developed tumors with latency of 9 to 25 weeks. raf oncogene expression in cell lines established from tumor tissues (lung adenocarcinoma and lymphomas) were initially determined by indirect immunofluorescence, and both tumor types were found to be positive. In preliminary experiments it was observed that vaccination with v-raf protein doubled the life expectancy of mice treated with both ENU and BHT. A significant increase in disease latency upon vaccination was also observed with mice treated with ENU only.
