Hyperoxia-induced DNA damage causes decreased DNA methylation in human lung epithelial-like A549 cells.

The effect of hyperoxia on levels of DNA damage and global DNA methylation was examined in lung epithelial-like A549 cells. DNA damage was assessed by the single-cell gel electrophoresis (comet assay) and DNA methylation status by the cytosine extension assays. Cells exposed to ionizing radiation (0, 1, 2, 4, or 8 Gy) showed increasing rates of percentage of DNA in the tail and tail length with increasing radiation dose. When cells were exposed to room air (normoxia) for 1 day and 95% O2 (hyperoxia) for 1, 2, 3, 4, and 5 days, data indicated that hyperoxia caused time-dependent increases in levels of (a) single strand breaks, (b) double strand breaks, and (c) 8-oxoguanine. Decreased DNA methylation also was observed at day 5 of hyperoxic exposure, suggesting that hyperoxia-induced DNA damage can influence patterns of DNA methylation in a lung-derived cell line.

[1]  H. Ischiropoulos,et al.  Transient injury to rat lung mitochondrial DNA after exposure to hyperoxia and inhaled nitric oxide. , 2004, American journal of physiology. Lung cellular and molecular physiology.

[2]  M. Szyf,et al.  The Methyl Donor S-Adenosylmethionine Inhibits Active Demethylation of DNA , 2003, Journal of Biological Chemistry.

[3]  M. Szyf,et al.  Epigenomic Stress Response , 2003, The Journal of Biological Chemistry.

[4]  M. O’Reilly,et al.  Growth arrest in G1 protects against oxygen‐induced DNA damage and cell death , 2002, Journal of cellular physiology.

[5]  G. Pfeifer,et al.  Oxidative DNA damage induced by copper and hydrogen peroxide promotes CG-->TT tandem mutations at methylated CpG dinucleotides in nucleotide excision repair-deficient cells. , 2002, Nucleic acids research.

[6]  M. Ehrlich,et al.  DNA methylation in cancer: too much, but also too little , 2002, Oncogene.

[7]  Min Wu,et al.  Protection of human lung cells against hyperoxia using the DNA base excision repair genes hOgg1 and Fpg. , 2002, American journal of respiratory and critical care medicine.

[8]  Esteban Ballestar,et al.  The impact of chromatin in human cancer: linking DNA methylation to gene silencing. , 2002, Carcinogenesis.

[9]  Peter A. Jones,et al.  Cell division is required for de novo methylation of CpG islands in bladder cancer cells. , 2002, Cancer research.

[10]  Albert Jeltsch,et al.  Beyond Watson and Crick: DNA Methylation and Molecular Enzymology of DNA Methyltransferases , 2002, Chembiochem : a European journal of chemical biology.

[11]  K. Albertine,et al.  DNA oxidation or apoptosis: will the real culprit of dna damage in hyperoxic lung injury please stand up? , 2002, American journal of respiratory cell and molecular biology.

[12]  R. Auten,et al.  Blocking neutrophil influx reduces DNA damage in hyperoxia-exposed newborn rat lung. , 2002, American journal of respiratory cell and molecular biology.

[13]  D. Jones,et al.  Activation of the p53 DNA damage response pathway after inhibition of DNA methyltransferase by 5-aza-2'-deoxycytidine. , 2001, Molecular pharmacology.

[14]  M. Szyf,et al.  DNA Methyltransferase Inhibition Induces the Transcription of the Tumor Suppressor p21 WAF1/CIP1/sdi1 * , 2000, The Journal of Biological Chemistry.

[15]  C Helma,et al.  A public domain image-analysis program for the single-cell gel-electrophoresis (comet) assay. , 2000, Mutation research.

[16]  K D Robertson,et al.  DNA methylation: past, present and future directions. , 2000, Carcinogenesis.

[17]  J. Herman,et al.  Hypermethylation of tumor suppressor genes in cancer. , 1999, Seminars in cancer biology.

[18]  I. Pogribny,et al.  A sensitive new method for rapid detection of abnormal methylation patterns in global DNA and within CpG islands. , 1999, Biochemical and biophysical research communications.

[19]  M. Panayiotidis,et al.  Glucose oxidase-produced H2O2 induces Ca2+-dependent DNA damage in human peripheral blood lymphocytes. , 1999, Free radical biology & medicine.

[20]  Hung D. Nguyen,et al.  DNA methylation differences associated with tumor tissues identified by genome scanning analysis. , 1998, Genomics.

[21]  P. Jones,et al.  Inhibition of DNA methylation by 5-aza-2'-deoxycytidine suppresses the growth of human tumor cell lines. , 1998, Cancer research.

[22]  B. Stripp,et al.  Exposure to hyperoxia induces p53 expression in mouse lung epithelium. , 1998, American journal of respiratory cell and molecular biology.

[23]  M. Dusinska,et al.  Comet assay in human biomonitoring studies: Reliability, validation, and applications , 1997, Environmental and molecular mutagenesis.

[24]  A. Collins,et al.  Ex vivo assessment of lymphocyte antioxidant status using the comet assay. , 1997, Free radical research.

[25]  A. Collins,et al.  Oxidative damage to DNA: do we have a reliable biomarker? , 1996, Environmental health perspectives.

[26]  J. Gardner,et al.  ATP-dependent Regulation of Sodium-Calcium Exchange in Chinese Hamster Ovary Cells Transfected with the Bovine Cardiac Sodium-Calcium Exchanger (*) , 1995, The Journal of Biological Chemistry.

[27]  P. R. Gardner,et al.  Aconitase is a sensitive and critical target of oxygen poisoning in cultured mammalian cells and in rat lungs. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[28]  Arthur S Slutsky,et al.  A critical role for thiol, but not ATP, depletion in 95% O2-mediated injury of preterm pneumocytes in vitro. , 1994, Archives of biochemistry and biophysics.

[29]  S. Weitzman,et al.  Free radical adducts induce alterations in DNA cytosine methylation. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[30]  M. Green,et al.  The single cell gel electrophoresis assay (comet assay): a European review. , 1993, Mutation research.

[31]  M. Cacciuttolo,et al.  Hyperoxia induces DNA damage in mammalian cells. , 1993, Free radical biology & medicine.

[32]  G. Satta,et al.  Protooncogene methylation and expression in regenerating liver and preneoplastic liver nodules induced in the rat by diethylnitrosamine: effect of variations of S-adenosylmethionine:S-adenosylhomocysteine ratio. , 1989, Carcinogenesis.

[33]  G. Catravas,et al.  The Effect of γ Radiation on DNA Methylation , 1989 .

[34]  E. Mullaart,et al.  Chromosomal instability in an oxygen-tolerant variant of Chinese hamster ovary cells. , 1989, Mutation research.

[35]  F. Becker,et al.  Perturbation of maintenance and de novo DNA methylation in vitro by UVB (280-340 nm)-induced pyrimidine photodimers. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[36]  Peter A. Jones,et al.  Inhibition of DNA methylation by chemical carcinogens in vitro , 1983, Cell.

[37]  J. Crapo,et al.  Biology of disease: free radicals and tissue injury. , 1982, Laboratory investigation; a journal of technical methods and pathology.

[38]  J. Crapo,et al.  Hyperoxia increases H2O2 release by lung mitochondria and microsomes. , 1982, Archives of biochemistry and biophysics.

[39]  J. Crapo,et al.  Hyperoxia increases oxygen radical production in rat lungs and lung mitochondria. , 1981, The Journal of biological chemistry.

[40]  L. M. Fairchild,et al.  Breakage of Chromosomes by Oxygen. , 1952, Proceedings of the National Academy of Sciences of the United States of America.