Ha-ras oncogene mutations in cell lines derived from rat tracheal implants exposed in vivo to 7,12-dimethylbenz[a]anthracene.
The frequency of Ha-ras mutations was determined as a function of neoplastic progression in cell lines derived from rat tracheal implants exposed in vivo to 7,12-dimethylbenz[a]anthracene. Restriction fragment-length polymorphism (RFLP) analysis revealed an A----T transversion in the second base of codon 61 in 2 of 11 cell lines. One of the positive cell lines was tumorigenic, but the other was neither tumorigenic nor anchorage independent, thus indicating a lack of correlation between neoplastic stage and ras mutation. Densitometry analysis of the RFLP bands indicated that approximately 50% of the cells within these two heterogeneous populations contained the mutation. Direct sequence analysis of polymerase chain reaction-amplified DNA confirmed these results and did not reveal any other mutations in this region of the Ha-ras gene.
Cosma
G N
GN
Institute of Environmental Medicine, New York University Medical Center, New York 10016.
Wirgin
I I
II
Marchok
A C
AC
Garte
S J
SJ
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000494:pharmacology*; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D003062:Codon; D004273:DNA, Neoplasm / Q000235:genetics; D004848:Epithelium / Q000187:drug effects; D008969:Molecular Sequence Data; D016296:Mutagenesis / Q000187:drug effects; D009154:Mutation; D009857:Oncogenes; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*; D051381:Rats; D011916:Rats, Inbred F344; D014132:Trachea / Q000187:drug effects*
D003062:Codon; D004273:DNA, Neoplasm; D015127:9,10-Dimethyl-1,2-benzanthracene; D016283:Proto-Oncogene Proteins p21(ras)