Causes, Smoking: "Smoking gun"
This section reviews K-ras and p53, two genes most frequently mutated in smoking-related lung cancers, one tar component, benzo[a]pyrene, is specifically linked to known mutations in these genes.
â€œSmoking gunâ€ K-ras and p53 are the two genes most frequently mutated in smoking-related lung cancers. One tar component, benzo[a]pyrene, is specifically linked to known mutations in these genes â€“ providing the equivalent of a "smoking gun" at a murder scene. Within a lung cell, benzo[a]pyrene is converted to an epoxide. The epoxide reacts readily with guanine (G) positions of the DNA helix. If not corrected by the cell's DNA repair mechanism, this guanine â€œadductâ€ is misread as a thymine by the DNA polymerase that copies chromosomes during replication. Ultimately, the original G-C base pair may be replaced by a T-A base pair, a mutation called a transversion. Cultured cells treated with benzo[a]pyrene show the same spectrum of G-T transversions as found in the k-ras and p53 genes of smokers. These mutational â€œhot spotsâ€ map well to the guanine binding sites of benzo[a]pyrene expoxide. Benzo[a]pyrene can produce the major known activating mutation in the 12th codon of the K-ras gene. Benzo[a]pyrene can also mutate three key positions in the p53 gene.
- ID: 958
- Source: DNALC.IC