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.

Figures

Figure 1

Structures of compounds discussed in the text with respect to quantitation of parent compounds and metabolites in the urine of people who use tobacco products.

Figure 2

Structures of DNA adducts reported in human lung tissue, using structure-specific methods (adapted from ). Mono-substituted dGuo adducts are to the left of the vertical line, and all others to the right. The following DNA adducts have also been detected in DNA from human oral tissue or saliva: 15, 19, 20, 21, 23, 24, 27, 28, 31, and 32.

Figure 3

Structures of DNA adducts reported in human saliva, but not in human lung.