DNA damage in the nasal passageway: a literature review

The purpose of this review is to provide a compilation of work examining DNA damage in the nasal cavity. There are numerous methods to identify and quantify damage to DNA and the diversity of methods and toxicologic endpoints is illustrated by the range of studies presented here. There are a large number of independent studies measuring endpoints in the upper respiratory tract; however, with regard to toxicant induced DNA damage in the nasal passageway, the effects of two compounds, 4-(N-Methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and formaldehyde (HCHO), appear to have been extensively characterized. The body of work on NNK and formaldehyde have provided insights into molecular mechanisms of DNA damage and repair and induced cell replication and its relationship to nasal cancer. With new technologies and molecular techniques, the sensitivity to enable evaluations of the minute quantities of nasal tissue available in test species and human biopsy impact the study of the nasal-toxicant interactions. As methods used to characterize DNA damage increase in sensitivity, the importance of both exogenous and endogenous sources of DNA damage, steady-state levels of cellular damage, repair, and resulting mutations, low-dose exposure assessments and inter-species extrapolation will become increasingly complex. Additional studies of DNA damage in the nasal passage will undoubtedly challenge future estimations of risk and impact what are perceived to be acceptable levels of exposure to known and predicted carcinogens. The aim of this paper is to provide to the interested scientist literature relevant to the effects of agents on nasal DNA, so that areas of insufficient information can be identified and used to further develop and expand the knowledge base for nasal DNA toxicant interactions.