HISTONE AND DNA ADDUCTS IN HUMAN LUNG CELLS

点击翻译按钮获取中文摘要

The overall objective of this project is the development and application of analytical methods for the detection of human pulmonary exposure to active metabolites of mutagenic and carcinogenic polycyclic aromatic hydrocarbons, including benzo[a]pyrene, cyclopental[cd]pyrene, fluoranthene, and other prominent mutagens discovered by this program project. DNA and histone adducts of the PAH will be determined in three types of human lung tissue:surgically derived bulk tissue, bronchial epithelial cells obtained by brush biopsy, and anatomically dissected whole lungs. Histone adducts will be assayed by cryogenic fluorescence line narrowing spectrometry and gas chromatography-mass spectrometry. DNA adducts will be assayed by a newly developed 35S-post labelling technique. The results will be compared with enzyme activities, mutational spectra, and localization of specific mutations determined by the other projects to develop an understanding of the role that chemical carcinogen adducts play in the development of human lung cancer.