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.
Wang
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Institute of Toxicology and Environmental Health, University of California, Davis 95616, USA.
Witschi
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H
D000818:Animals; D001483:Base Sequence; D002084:Butylated Hydroxytoluene; D011905:Genes, ras; D008175:Lung Neoplasms / Q000139:chemically induced / Q000235:genetics*; D008297:Male; D008748:Methylcholanthrene; D051379:Mice; D008969:Molecular Sequence Data; D010323:Passive Cutaneous Anaphylaxis; D017354:Point Mutation; D014520:Urethane
D002084:Butylated Hydroxytoluene; D014520:Urethane; D008748:Methylcholanthrene