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Recent studies indicate that the prevailing concept of decreased bioactivation of the normally lethal dose of CCl<jats:sub>4<\/jats:sub> owing to decreased hepatic microsomal cytochrome P\u2010450<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"#note1\"\/><jats:fn><jats:p>Abbreviations used: CD, chlordecone; cyt. P\u2010450, cytochromes P\u2010450; M, mirex; N, normal diet; PB, phenobarbital.<\/jats:p><\/jats:fn>\n content can not be supported by direct end points of liver injury such as necrosis. These findings suggest a pivotal role for hepatocellular division and tissue healing processes stimulated by the protective dose in the mechanism of autoprotection. Augmentation of hepatocellular regeneration and tissue repair, stimulated by the protective dose, appears to permit timely recovery and restoration of hepatic structure and function. In the absence of the protective dose, hepatocellular division is substantially deficient and it occurs too late to tip the delicate balance between recovery from injury and progression of massive injury in favor of recovery. Abolition of autoprotection by colchicine antimitosis, under conditions where metabolism and disposition of CCl<jats:sub>4<\/jats:sub> are not altered, is supportive of this concept. Selective colchicine antimitotic suppression of the early phase of hepatocellular division and tissue repair induced by a low dose of CCl<jats:sub>4<\/jats:sub> results in progression of toxic liver injury, leading to hepatic failure and mortality. Studies have shown that pretreatment with phenobarbital results in postponed low\u2010dose CCl<jats:sub>4<\/jats:sub>\u2010stimulated cell division by 24 hours, which accordingly postpones the optimal autoprotection. These findings provide discrete evidence to suggest that the protective dose\u2010stimulated hepatocellular division and tissue repair underlies the mechanism of autoprotection. These new insights reveal that in contrast to the widely held concept, the ultimate outcome of toxic injury is determined by whether a prompt stimulation of sustainable tissue repair can occur rather than by the magnitude of the injury inflicted by a toxic chemical.<\/jats:p>","DOI":"10.1002\/jbt.2570090304","type":"journal-article","created":{"date-parts":[[2006,10,18]],"date-time":"2006-10-18T02:04:40Z","timestamp":1161137080000},"page":"131-139","source":"Crossref","is-referenced-by-count":35,"title":["Autoprotection: Stimulated tissue repair permits recovery from injury"],"prefix":"10.1002","volume":"9","author":[{"given":"Harihara M.","family":"Mehendale","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kashyap N.","family":"Thakore","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C. 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