Oral Cell DNA Adducts as Potential Biomarkers for Lung Cancer Susceptibility in Cigarette Smokers

Abstract

This perspective considers the use of oral cell DNA adducts, together with exposure and genetic information, to potentially identify those cigarette smokers at highest risk for lung cancer, so that appropriate preventive measures could be initiated at a relatively young age before too much damage has been done. There are now well established and validated analytical methods for the quantitation of urinary and serum metabolites of tobacco smoke toxicants and carcinogens. These metabolites provide a profile of exposure and in some cases lung cancer risk. But they do not yield information on the critical DNA damage parameter that leads to mutations in cancer growth control genes such as KRAS and TP53. Studies demonstrate a correlation between changes in the oral cavity and lung in cigarette smokers, due to the field effect of tobacco smoke. Oral cell DNA is readily obtained in contrast to DNA samples from the lung. Studies in which oral cell DNA and salivary DNA have been analyzed for specific DNA adducts are reviewed; some of the adducts identified have also been previously reported in lung DNA from smokers. The multiple challenges of developing a panel of oral cell DNA adducts that could be routinely quantified by mass spectrometry are discussed.

Comet and micronucleus assays do not correlate extent of DNA damage with clinical staging of oral cavity squamous cell carcinoma

“…The first contact of potential genotoxic agents with the oral cavity occurs in the oral mucosa 22 . Genotoxic agents such as alcohol and cigarette components may trigger carcinogenesis 4,23 , including OCSCC 5,24 .…”

DNA adducts: Formation, biological effects, and new biospecimens for mass spectrometric measurements in humans

“…32 P‐postlabeling, GC/MS, and LC/MS methods require that the DNA is broken down to the single adducted nucleobase, either by nucleases, heat or acid treatment, whereas, immuno‐detection methods employ the intact DNA and probe for lesions with antibodies raised against specific carcinogen adducts . DNA adducts have been detected in a wide range of tissues, white blood cells, oral cells, and exfoliated cells in urine . The use of cells may be appropriate for estimating exposure and DNA damage in target tissues, but extrapolations must be made with caution.…”

Molecular and health effects in the upper respiratory tract associated with tobacco smoking other than cigarettes

“…DNA adduct levels in pipe and cigar smokers are lower than in cigarette smokers but higher that in nonsmokers. Altogether it indicates how harmful is deep inhaling of tobacco smoke …”

“…Altogether it indicates how harmful is deep inhaling of tobacco smoke. 63,64 ROS generate DNA damage in two ways. First, high reactivity of ROS induces damage to all purines and pyrimidines as well as to the deoxyribose and phosphate backbone.…”