mortality/aging
• mice are more sensitive to acetaminophen-induced lethality compared with similarly treated wild-type mice
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homeostasis/metabolism
• in acetaminophen-treated mice
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• increased cadmium sensitivity
• take up a hunched back posture, ruffed coat and display general lethargy
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• acetaminophen-induced lipid peroxidation is increased compared to in similarly treated wild-type mice
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• mice are more sensitive to acetaminophen-induced lethality compared with similarly treated wild-type mice
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• mice exhibit increased susceptibility to acetaminophen-induced hepatotoxicity, alanine aminotransferase, hepatic necrosis, lipid peroxidation, and lethality compared with similarly treated wild-type mice
• acetaminophen-induced injuries are not ameliorated by pretreatment with zinc unlike in similarly treated wild-type mice
• however, acetaminophen metabolism is normal
• hepatocytes are more sensitive to acetaminophen and NAPQI-induced oxidative stress compared with similarly treated wild-type cells
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• increased sensitivity to DMBA/TPA treatment; 100% of treated mice have tumors by 19 weeks, and only 10% of wild-type mice have tumors at 20 weeks, and the average tumor size of treated mice is 2X larger
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liver/biliary system
• hepatocytes are more sensitive to acetaminophen and NAPQI-induced oxidative stress indicated by lactate dehydrogenase leakage compared with similarly treated wild-type cells
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• in acetaminophen-treated mice
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neoplasm
• 90% of mice with tumors by 13 weeks (earliest tumors by 9 weeks)
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• increased sensitivity to DMBA/TPA treatment; 100% of treated mice have tumors by 19 weeks, and only 10% of wild-type mice have tumors at 20 weeks, and the average tumor size of treated mice is 2X larger
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