OXIDATIVE DNA-DAMAGE IN HUMAN RESPIRATORY-TRACT EPITHELIAL-CELLS - TIME-COURSE IN RELATION TO DNA STRAND BREAKAGE

When human respiratory tract epithelial cells were exposed to 100 mu M H2O2, there was rapid induction of DNA strand breakage and chemical m odifications to all 4 DNA bases suggestive of attack by OH.. The major products were FAPy-adenine, FAPy-guanine, and 8-OH-guanine. Some of t he base modifications were removed very quickly from the DNA (e.g., 8- OH-guanine), whereas others persisted for longer (e.g., thymine glycol ), probably due to differential activity of different repair enzymes. By contrast, strand breaks continued to increase over the time course of the experiment, perhaps because strand breakage is also implicated in the repair process. One should therefore be cautious in using stran d breakage as a sole measure of oxidative DNA damage, and when drawing conclusions about the pattern and biological significance of oxidativ e DNA damage in cells the relative persistence of different lesions mu st be considered. (C) 1996 Academic Press, Inc.