title: Induction of chronic oxidative stress, chronic inflammation and aberrant patterns of DNA methylation in the liver of titanium-exposed CBA/CaJ mice.
abstract: OBJECTIVE
  To investigate the biological effects of titanium ((48)Ti, one of the important heavy ions found in space) in the liver of exposed-mice.
  
  
  METHODS
  We gave adult male CBA/CaJ mice a whole-body exposure to a total dose of 0, 0.1, 0.25 or 0.5 Gy of (48)Ti ions. The liver was collected at 1 week, 1 month, and 6 months post-irradiation (five mice per treatment-group at each harvest-time). Three biological endpoints were used for evaluating the effects of (48)Ti ions: Oxidative-stress, inflammatory responses, and DNA-methylation (5-methylcytosine and 5-hydroxymethylcytosine).
  
  
  RESULTS
  Our data clearly demonstrated dose-dependent increases in oxidative stress and inflammatory responses in the liver of exposed mice at all time-points (Analysis of Variance or ANOVA, p < 0.05). Significant dose-dependent increases in the levels of 5-methylcytosine were detected at 1 week and 1 month (ANOVA, p < 0.05). At 6 months post-irradiation, a significant increase in the level of 5-methylcytosine was found only in 0.5-Gy-(48)Ti-ion-exposed mice. In contrast, dose-dependent decreases in 5-hydroxymethylcytosine levels were found in the liver of exposed mice (ANOVA, p < 0.05) at all time-points.
  
  
  CONCLUSIONS
  Chronic oxidative-stress, chronic inflammation, and persistent aberrant DNA-methylation occurred in the liver of (48)Ti-exposed mice. Hence, exposure to (48)Ti ions in space may pose health risks.
authors.affiliation: Pathology Department, Stony Brook University , Stony Brook, NY , USA.
authors.forename: Witawat
authors.initials: W
authors.lastname: Jangiam
authors.forename: Montree
authors.initials: M
authors.lastname: Tungjai
authors.forename: Kanokporn Noy
authors.initials: KN
authors.lastname: Rithidech
mesh_terms: D044503:5-Methylcytosine / Q000378:metabolism / Q000031:analogs & derivatives; D000818:Animals; D043171:Chromosomal Instability / Q000528:radiation effects; D003596:Cytosine / Q000031:analogs & derivatives / Q000378:metabolism; D019175:DNA Methylation / Q000528:radiation effects*; D004307:Dose-Response Relationship, Radiation; D044127:Epigenesis, Genetic / Q000528:radiation effects; D006412:Hematopoietic Stem Cells / Q000378:metabolism / Q000528:radiation effects; D007249:Inflammation / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D015227:Lipid Peroxidation / Q000528:radiation effects; D008099:Liver / Q000378:metabolism* / Q000528:radiation effects*; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress / Q000528:radiation effects*; D013997:Time Factors; D014025:Titanium / Q000009:adverse effects*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D053583:Interleukin-1beta; D015850:Interleukin-6; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; C011865:5-hydroxymethylcytosine; D044503:5-Methylcytosine; D003596:Cytosine; D014025:Titanium
keywords: 5-hydroxymethylcytosine; 5-methylycytosine; In vivo oxidative stress; inflammatory responses; liver; titanium