Activating mutation of the Ha-ras gene in chemically induced tumors of the hamster cheek pouch.
The presence of an activating mutation in the Ha-ras gene in hamster cheek pouch tumors induced by 7,12-dimethylbenz[a]anthracene (DMBA) complete carcinogenesis was investigated. The normal sequence of a fragment of genomic DNA encompassing codon 61 of the Ha-ras gene was amplified by the polymerase chain reaction using primers designed for a highly conserved region of the mouse Ha-ras-1 gene. The sequence of the amplified fragment was determined by a direct sequencing technique and exhibited 83.3% and 87.5% homology with the corresponding human and mouse sequences, respectively. At the amino acid level, the sequence was identical among the three species. Paraffin sections of 11 squamous cell carcinomas of the cheek pouch were used to detect mutated Ha-ras alleles. DNA sequencing of the tumors showed that six of 11 tumors presented an A----T transversion in the second position of codon 61, resulting in an amino acid change from glycine to leucine. As has been demonstrated in other systems, we have shown a specific mutation of the Ha-ras gene in chemically induced tumors of the hamster cheek pouch, further supporting the role of this oncogene in chemical carcinogenesis.
Gimenez-Conti
I B
IB
Science Park-Research Division, University of Texas M. D. Anderson Cancer Center, Smithville 78957.
Bianchi
A B
AB
Stockman
S L
SL
Conti
C J
CJ
Slaga
T J
TJ
D015127:9,10-Dimethyl-1,2-benzanthracene; D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D006224:Cricetinae; D004252:DNA Mutational Analysis; D011905:Genes, ras; D006801:Humans; D008647:Mesocricetus; D051379:Mice; D008969:Molecular Sequence Data; D009062:Mouth Neoplasms / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D016296:Mutagenesis; D009838:Oligodeoxyribonucleotides; D016133:Polymerase Chain Reaction; D012689:Sequence Homology, Nucleic Acid
D009838:Oligodeoxyribonucleotides; D015127:9,10-Dimethyl-1,2-benzanthracene