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-

Accumulation of Copper Induces DNA Strand Breaks in Brain Cells of Long-Evans Cinnamon (LEC) Rats, An Animal Model for Human Wilson Disease

“…400 ppm at 20 weeks of age. These results are essentially in good agreement with our previous results [8,10,11]. No significant differences were found between iron contents in the three regions of brains of WKAH and LEC rats from 4 to 26 weeks of age (Fig.…”

“…These results show that SSBs of DNA were produced in the cerebrum and cerebellum cells of LEC rats at 24 weeks of age. Since SSBs of DNA were induced in a substantial population of LEC rat liver and kidney cells at 10 and 12 weeks of age, respectively [8,10,11], production of DNA SSBs in the brain cells occurred at a late age compared with the age at which DNA SSBs were induced in the liver and kidney cells of LEC rats. It has been reported that iron also accumulates in the liver of LEC rats and that hepatic iron may be an additional important factor contributing to liver injury in LEC rats [14,15].…”

“…However, since no significant differences were found between iron contents in the three regions of the brain of WKAH and LEC rats from 4 to 26 weeks of age, the production of SSBs in brain cells of LEC rats may be due to accumulation of copper, not iron. Although high concentrations of copper (200-400 ppm) are necessary for production of SSBs in hepatic and renal cells [8,10,11], SSBs in brain cells were produced at low concentrations of copper (8.5-16 ppm). It is thought that the brain is highly sensitive to ROS because of its high oxygen utilization, high concentration of polyunsaturated fatty acids and low concentrations of cytosolic antioxidants [7].…”

“…It has been shown that ROS induce several types of DNA damage, such as base alteration and DNA strand breaks [16,42,49]. We showed that DNA strand breaks are induced in hepatic and renal cells of LEC rats by copper accumulation [8,10,11]. The amounts of 8-hydroxydeoxyguanosine (oh 8 dG) in DNA, a marker of ROS-derived DNA damage, in the liver and kidney of LEC rats were significantly higher than those of control rats at 15 weeks of age, but no significant differences were found between the amounts of oh 8 dG in DNA in the brains of LEC and control rats from 4 to 26 weeks of age [48].…”

Radiofrequency Radiation at 40kHz Induces Hepatic Injury in Long-Evans Cinnamon (LEC) Rats, an Animal Model for Human Wilson Disease

“…Copper contents: Since it is thought that copper that has accumulated in the liver is released from severely damaged hepatocytes into the blood and deposited in other organs, including the kidney [13,27], we examined the effects of RF radiation on copper contents in the liver, kidney and serum of LEC rats (Fig. 3).…”