Mouse liver cell lines that bear a stably integrated lactose operon re
pressor (lacI) gene and a Ha-ras gene linked to a lactose operator-con
taining SV40 early promoter were generated. When grown in medium conta
ining more than 0.1 mM isopropyl beta-D-thiogalactoside (IPTG), the Ha
-ras gene was induced up to 20-fold. Maximum induction of Ha-ras gene
expression occurred after 12 h of exposure. The tumorigenicity of thes
e cell lines in syngeneic mice was enhanced when the mice were maintai
ned on drinking water containing 12.5 mM IPTG, Ha-ras gene expression
in tumors was strongly induced in the presence of IPTG in vivo. Induct
ion of Ha-ras gene expression in mice was consistently observed after
48 hr of exposure to drinking water containing IPTG. This system provi
des an approach for studying the function of oncogene in vivo as well
as other genes of interest.