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 12/13. 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 12/13 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.