| 20155282 |
Irie H, Asano-Hoshino A, Sekino Y, Nogami M, Kitagawa T, Kanda H: Striking LD (50) variation associated with fluctuations of CYP2E1-positive cells in hepatic lobule during chronic CCl (4) exposure in mice. Virchows Arch. 2010 Feb 13.
Intraperitoneal injection of serially diluted carbon tetrachloride (CCl (4)) from 0.2 to 2.0 ml/kg produced an LD (50) value of 0.46 ml/kg in the normal mouse. Following repeated administration of 0.2 ml/kg CCl (4) twice a week for 1 and 3 months, the LD (50) values were over 2.0 and 0.72 ml/kg, respectively. A single administration of 0.2 ml/kg CCl (4) induced, within 24 h, apoptotic death of liver cells in the centrilobular zone 3 that were observed positive in cytochrome P450 2E1 (CYP2E1). However, after repeated exposure to 0.2 ml/kg twice a week for 1 month, cells in the centrilobular area were almost completely replaced with CYP2E1-negative cells. These cells were tolerant to CCl (4). After 3 months of exposure, a considerable number of CYP2E1-positive hepatocytes were observed throughout the periportal zone 1 and intermediate zone 2. Thus, fluctuations in CYP2E1-positive cells during chronic exposure to low doses of CCl (4) induced tolerance, which can be partially lost after prolonged CCl (4) exposure. |
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