DNA adduct formation in the human nasal mucosa as a biomarker of exposure to environmental mutagens and carcinogens

Abstract

Human exposure to chemical compounds, often termed xenobiotics, has been linked to a number of enhanced incidences of various neoplasias. A majority of these enter the human body through inhalation. Most xenobiotics are metabolized in the body to more hydrophilic metabolites before excretion in the urine and bile. During this process, promutagens and procarcinogens could be activated and could interact with proteins as well as DNA to form adducts. DNA adducts formed by chemical carcinogens can, therefore, be used as biomarkers of exposure and other host factors. This study that DNA adduct analysis can be performed on cells from human nasal mucosa. Using the nasal lavage procedure performed on 20 healthy volunteers, 5 x 10(5) to 5 x 10(6) cells were obtained from which 5 to 40 micrograms DNA was isolated. DNA adducts were analyzed by the 32-P-postlabeling assay. The DNA adduct levels ranged between 1.4 and 6 adducts/10(8) nucleotides. In addition to its simplicity, the nasal lavage procedure is an inexpensive, noninvasive procedure that requires no anesthetics or special equipment. Moreover, the cells obtained are the first to come in contact with air pollutants. DNA adduct analysis from human nose mucosa cells could therefore be used to develop a technique suitable for the assessment of exposure to chemical carcinogens through inhalation.