These adducts will form at guanine bases in DNA. Normally, guanine will pair with cytosine in the DNA helix, but when the DNA adduct has replicated the enzymes that do the copying will put an adenine base opposite of the guanine. These point mutations are called G-to-T transversions. Single purine bases are changed for a pyrimidine or vice versa. An abundance of these G-to-T transversions in DNA is an indicator of smoking-induced damage. 

DNA-Carcinogen Adducts

Carcinogens liken to target the tumor suppressor genes or oncogenes primarily. Mutations that occur on the p53 tumor suppressor gene are common in smokers and the lungs. An excess of G-to-T transversions occurs for these tumors that grow here. Around 30% of the point mutations that happen on this gene are the G-toT transversions (in smokers), as compared to 12% in non-smokers. Nonsmokers have an increased number of G to A transversions (47% to 27% smokers). 



Carcinogen Targets

One of the most studied PAHs, benzo[a]pyrene (BaP) can cause genotoxic changes to DNA. When BaP enters the body it will be processed by enzymes which will allow it to become water soluble. These water soluble forms of the BaP will be called epoxides. Epoxides are good at binding to DNA and creating the bulky adducts. When adducts remain attached, they generally form in the lungs, mouth, and bladder for smoking-induced cancers. 

State University of New York at Stony Brook

Many of the carcinogens that are found in tobacco smoke can also be found in grilled foods, engine exhaust, and the general environment. There are certain tobacco specific PAHs such as benzo[a]pyrene (BaP) and N-nitrosamine, NNK (4-(methylnitrosamino)-1-(3-pyridyl)-1- butanone). 


How do we know that the carcinogens are tobacco specific? 


Matthew Tontonoz Friday, D. 7. (2018, December 07). How Do Cigarettes Cause Cancer? Retrieved from https://www.mskcc.org/news/how-do-cigarettes-cause-cancer


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