Inhibitory effects of trientine, a copper-chelating agent, on induction of DNA strand breaks in hepatic cells of Long-Evans Cinnamon rats.
Effects of treatment with trientine, a specific copper-chelating agent, on accumulation of copper and induction of DNA strand breaks were investigated in Long-Evans Cinnamon (LEC) rats, an animal model for human Wilson's disease. Copper accumulated in the livers of LEC rats in an age-dependent manner from 4 to 13 weeks of age. When LEC rats were treated with trientine from 10 weeks of age, hepatic copper contents did not increase and were maintained at the same levels as those in 10-week-old LEC rats. When the amounts of DNA single-strand breaks (SSBs) were estimated by a comet assay, SSBs of DNA were induced in a substantial population of LEC rat hepatic cells around 8 weeks of age and the amounts of SSBs increased in an age-dependent manner from 8 to 15 weeks of age. When LEC rats were treated with trientine from 10 weeks of age, the observed number of cells with DNA damage decreased dramatically, suggesting that induction of SSBs of DNA was inhibited and/or SSBs were repaired during the period of treatment with trientine. The results show that treatment of LEC rats with trientine decreases the number of DNA strand breaks observed, although copper contents remain high in the liver.
Hayashi
Masanobu
M
Department of Veterinary Radiology, School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu 069-8501, Japan. hayashi@rakuno.ac.jp
Miyane
Kazuhiro
K
Hirooka
Takeshi
T
Endoh
Daiji
D
Higuchi
Hidetoshi
H
Nagahata
Hajime
H
Nakayama
Kenji
K
Kon
Yashuhiro
Y
Okui
Toyo
T
D000375:Aging; D000818:Animals; D002469:Cell Separation / Q000379:methods; D004249:DNA Damage / Q000187:drug effects*; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D008668:Metallothionein / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D020332:Rats, Inbred LEC; D014266:Trientine / Q000494:pharmacology*
D008668:Metallothionein; D014266:Trientine