title: Tissue-dependent preventive effect of metallothionein against DNA damage in dyslipidemic mice under repeated stresses of fasting or restraint.
abstract: OBJECTIVE
  To investigate the effect of repeated stress on DNA damage in seven organs of dyslipidemic mice, and the preventive role of metallothionein (MT).
  
  
  METHODS
  Female adult 129/Sv wild-type and MT-null mice fed high-fat diet (HFD) were repeatedly subjected to mild stress of fasting or restraint in weeks 2 to 4 of 4-week study period. Serum cholesterol level, DNA damage in the liver, pancreas, spleen, bone marrow, kidney, lung and gastric mucosa, and other parameters were determined.
  
  
  RESULTS
  Body weights were increased in both types of mice fed HFD compared to those fed standard diet (STD), and further increased by 12 h-fasting, while they were markedly decreased by 1-3 h-restraint. Fasting accelerated accumulation of fat in the liver, and increase in serum cholesterol of both types of mice fed HFD. Feeding of HFD increased DNA damage in the pancreas, spleen and bone marrow of both types of mice, compared with those fed STD. In the wild-type mice fed HFD, 24 h-fasting increased DNA damage in the liver and spleen, while restraint increased the damage in the liver, pancreas, spleen and bone marrow. DNA damage in the cells of organs was markedly increased in the MT-null mice. Specifically, damage in the liver, pancreas, spleen and bone marrow was greatly increased with the intensity of stress increased, and the damage was much greater in the restraint mice than in the fasting mice.
  
  
  CONCLUSIONS
  MT plays a tissue-dependent preventive role against DNA damage in various murine organs induced by repeated stress.
authors.affiliation: Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Yamashiro-cho, Tokushima 770-8514, Japan. togen@nagoya-ku.ac.jp
authors.forename: Minoru
authors.initials: M
authors.lastname: Higashimoto
authors.forename: Naohiro
authors.initials: N
authors.lastname: Isoyama
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ishibashi
authors.forename: Masahisa
authors.initials: M
authors.lastname: Inoue
authors.forename: Masufumi
authors.initials: M
authors.lastname: Takiguchi
authors.forename: Shinya
authors.initials: S
authors.lastname: Suzuki
authors.forename: Yoshinari
authors.initials: Y
authors.lastname: Ohnishi
authors.forename: Masao
authors.initials: M
authors.lastname: Sato
mesh_terms: D000818:Animals; D001835:Body Weight; D020552:Comet Assay; D004249:DNA Damage; D004041:Dietary Fats / Q000008:administration & dosage; D050171:Dyslipidemias / Q000235:genetics*; D005215:Fasting; D005260:Female; D005978:Glutathione / Q000378:metabolism; D007103:Immobilization; D008099:Liver / Q000378:metabolism; D008668:Metallothionein / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009929:Organ Size; D010179:Pancreas / Q000378:metabolism; D013312:Stress, Physiological
chemical_list: D004041:Dietary Fats; D008668:Metallothionein; D005978:Glutathione