HEPATOCELLULAR REGENERATION - KEY TO THIOACETAMIDE AUTOPROTECTION

Low doses of thioacetamide stimulate cell division and tissue repair i n the liver. The objective of this study was to develop an autoprotect ion model for thioacetamide and investigate if a low dose of thioaceta mide (50 mg/kg orally) protects against lethality of a subsequently ad ministered lethal dose (400 mg/kg orally) of the same compound. The ex tent of cell division was investigated to test if autoprotection resul ts from augmented tissue repair and recovery from injury rather than d ecreased injury itself. After a single administration of the protectiv e dose of thioacetamide, hepatocellular nuclear DNA synthesis as measu red by H-3-thymidine incorporation into hepatocellular nuclear DNA pea ked at 36 hr indicating maximum level of S-phase stimulation. Pretreat ment with the antimitotic colchicine abolished autoprotection and this was associated with a significantly decreased H-3-thymidine incorpora tion. preadministration of the protective dose of thioacetamide did no t result in an altered infliction of injury from the subsequently admi nistered lethal dose. Colchicine intervention in the autoprotected gro up resulted in injury that followed a pattern similar to the group tha t received the high dose alone, ultimately resulting in animal death. These findings suggest that cell division stimulated by the protective low dose of thioacetamide is the critical mechanism in thioacetamide autoprotection.