Lack of mutations in K-ras codons 12 and 13 in human atherosclerotic lesions.
In the framework of a project investigating the possible involvement of cancer biomarkers in human atherogenesis, we evaluated the occurrence of K-ras mutations in the DNA extracted from smooth muscle cells of abdominal aorta atherosclerotic lesions. The molecular analysis of the DNA from 32 surgical specimens, using PCR-based denaturing gradient gel electrophoresis (DGGE), did not reveal any variant in K-ras codons 12 and 13, which are the most frequently involved codons among the ras genes mutated in various types of human tumors. Analysis of the DNA extracted from four cell lines carrying known K-ras mutational alleles showed typically positive DGGE patterns. Thus, on the whole, the conclusions of this study and of previous studies using the same biological material are consistent with the occurrence of DNA adducts in human atherosclerotic lesions but in the absence of p53 involvement or of K-ras mutations in codons 12 and 13. The search for candidate genes which may possibly be involved in the atherogenetic process warrants further studies.
Bogliolo
M
M
Center for the Study of Tumors of Environmental Origin, National Institute for Cancer Research (IST), Genoa, Italy.
Fronza
G
G
Campomenosi
P
P
Assereto
P
P
Izzotti
A
A
Petrilli
G L
GL
Abbondandolo
A
A
De Flora
S
S
D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001012:Aorta, Abdominal / Q000737:chemistry; D001161:Arteriosclerosis / Q000235:genetics*; D001483:Base Sequence; D002460:Cell Line; D003062:Codon / Q000235:genetics*; D004247:DNA / Q000032:analysis / Q000302:isolation & purification; D005260:Female; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D009692:Nucleic Acid Heteroduplexes / Q000032:analysis; D016133:Polymerase Chain Reaction
D003062:Codon; D009692:Nucleic Acid Heteroduplexes; D004247:DNA