Tissue-dependent preventive effect of metallothionein against DNA damage in dyslipidemic mice under repeated stresses of fasting or restraint.
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.
Higashimoto
Minoru
M
Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Yamashiro-cho, Tokushima 770-8514, Japan. togen@nagoya-ku.ac.jp
Isoyama
Naohiro
N
Ishibashi
Satoshi
S
Inoue
Masahisa
M
Takiguchi
Masufumi
M
Suzuki
Shinya
S
Ohnishi
Yoshinari
Y
Sato
Masao
M
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
D004041:Dietary Fats; D008668:Metallothionein; D005978:Glutathione