Modulation of oxidative DNA damage repair by the diet, inflammation and neoplastic transformation.
Oxidative DNA damage and DNA repair may mediate several cellular processes, like replication and transcription, mutagenesis and apoptosis and thus may be important for the organism development as well as its pathogenesis, including cancer. Activity of DNA repair enzymes can depend on many factors, such as gene polymorphism, mRNA and protein level, as well as enzymes activation and inhibition. Modulation of base excision repair pathway eliminating from DNA oxidatively formed lesions may be caused by the diet, inflammation and neoplastic transformation. Reactive oxygen species and some diet components induce transcription of several Base Excision Repair enzymes, e.g. major human AP-endonuclease, (APE1) and 8-oxoG-DNA glycosylase (OGG1). The carcinogenic process in human lung decreases repair activity for 8-oxoGin transcription independent manner, but increases repair activity of epsilon A and epsilon C, as measured in tumors and unchanged lung tissues of lung cancer patients. Thus, modulation of repair enzymes activities may be a cell response on their way to differentiation ot neoplastic transformation.
Tudek
B
B
Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw, Poland. tudek@ibb.waw.pl
Swoboda
M
M
Kowalczyk
P
P
Oliński
R
R
D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D004249:DNA Damage; D004260:DNA Repair; D004032:Diet; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress