title: Inhibitory effects of trientine, a copper-chelating agent, on induction of DNA strand breaks in kidney cells of Long-Evans Cinnamon (LEC) rats.
abstract: The effects of treatment with trientine, a specific copper-chelating agent, on the 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 kidneys of LEC rats in an age-dependent manner from 12 to 18 weeks of age. When LEC rats were treated with trientine from 10 weeks of age, renal copper contents did not increase and were maintained at the same levels as those in 4-week-old LEC rats. Estimation of the amounts of DNA single-strand breaks (SSBs) by comet assay showed that SSBs of DNA were induced in a substantial population of LEC rat renal cortex cells around 12 weeks of age and that the amounts of SSBs increased in an age-dependent manner from 12 to 18 weeks of age. When LEC rats were treated with trientine from 10 weeks of age, the observed number of cells with DNA damage decreased, 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 SSBs of DNA in LEC rat kidney cells are induced prior to occurrence of clinical signs of hepatic injury and that treatment of LEC rats with trientine decreases the number of DNA strand breaks.
authors.affiliation: Department of Veterinary Radiology, School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu, Japan.
authors.forename: Masanobu
authors.initials: M
authors.lastname: Hayashi
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Miyane
authors.forename: Misato
authors.initials: M
authors.lastname: Senou
authors.forename: Daiji
authors.initials: D
authors.lastname: Endoh
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Higuchi
authors.forename: Hajime
authors.initials: H
authors.lastname: Nagahata
authors.forename: Kenji
authors.initials: K
authors.lastname: Nakayama
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kon
authors.forename: Toyo
authors.initials: T
authors.lastname: Okui
mesh_terms: D000284:Administration, Oral; D000818:Animals; D002374:Catalase / Q000378:metabolism; D002614:Chelating Agents / Q000494:pharmacology*; D020552:Comet Assay; D003300:Copper / Q000032:analysis / Q000378:metabolism*; D053904:DNA Breaks, Single-Stranded / Q000187:drug effects*; D004249:DNA Damage / Q000187:drug effects*; D007501:Iron / Q000032:analysis / Q000378:metabolism; D007668:Kidney / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051381:Rats; D020332:Rats, Inbred LEC; D013482:Superoxide Dismutase / Q000378:metabolism; D014266:Trientine / Q000494:pharmacology*
chemical_list: D002614:Chelating Agents; D003300:Copper; D007501:Iron; D002374:Catalase; D013482:Superoxide Dismutase; D014266:Trientine