Impaired DNA Synthesis by Copper Cytotoxicity in LEC Mutant Rat.
- Author:
Jin Kyung KIM
1
;
Young Mi KWON
;
Jae Min OH
Author Information
1. Department of Anatomy, School of Medicine, Wonkwang Medical Science Institute, Wonkwang University, Korea. jmoh@wonkwang.ac.kr
- Publication Type:Original Article
- Keywords:
Copper;
LEC mutant rat;
Histone;
Protein phosphorylation;
Toxicity
- MeSH:
Animals;
Cinnamomum zeylanicum;
Copper*;
DNA*;
Epidermal Growth Factor;
Hepatocytes;
Histones;
Insulin;
Nuclear Proteins;
Phosphorylation;
Rats*;
Rats, Inbred F344
- From:Korean Journal of Anatomy
2004;37(6):565-570
- CountryRepublic of Korea
- Language:English
-
Abstract:
Long-Evans Cinnamon (LEC) mutant rat, which spontaneously develops a necrotizing hepatic injury at 4 ~5 months of age, reveals an excess hepatic copper accumulation and is a good model for studying the detail mechanism of cellular copper toxicity. We have observed the effects of copper toxicity on DNA synthesis upon growth stimulation by treating primary-cultured hepatocytes of LEC rat with epidermal growth factor (EGF) and insulin. DNA synthesis measured by [ 3 H]-thymidine incorporation and DNA synthesis S-phase cells in LEC rat significantly decreased when compared to those of normal F344 rat. Since DNA synthesis was impaired in LEC rat, we examined the detail mechanism by determining the histone content, which are involved in DNA stability, and the phosphorylation of nuclear protein. However, the histone contents and phosphorylated nuclear protein upon growth stimulation was intact in LEC rat. These results suggest that a cellular event other than protein phosphorylation required for the initiation of DNA synthesis upon growth stimulation is impaired by copper cytotoxicity in LEC rat.
