Mutations of the Ki-ras protooncogene in 3-methylcholanthrene and urethan-induced and butylated hydroxytoluene-promoted lung tumors of strain A/J and SWR mice

Mutations of the Ki-ras protooncogene in 190 lung tumors initiated in male A/J and SWR mice by 3-methylcholanthrene(MCA) or urethan and promoted by butylated hydroxytoluene (BHT), were evaluated by utilizing polymerase chain reaction (PCR) and sequencing analysis. The most common mutation pattern was a GC to CG transversion at the first base of codon 1213. The predominant mutation pattern at codon 61 was an AT to TA transversion and the next frequent one an AT to GC transition. Mutations of Ki-ras codon 1213 were found in 44% (A/J) and 13% (SWR) of MCA-induced and in 94% (A/J) and 43%(SWR) of MCA plus BHT-induced lung tumors. Mutations of the Ki-ras codon 61 were found in 31%(A/J) and 13% (SWR) of urethan-induced and 69%(A/J) and 44%(SWR) of urethan plus BHT-induced lung tumors. These data suggest that in strain A/J mice the 2 carcinogens produce Ki-ras mutations and that BHT promotes the activations of Ki-ras protooncogenes in lung tumors.