1,1,2,2-TETRACHLOROETHANE-INDUCED EARLY DECREASE OF DOLICHOL LEVELS IN RAT-LIVER MICROSOMES AND GOLGI-APPARATUS

Dolichols are long-chain polyprenols containing 14-22 isoprene units, present in mammalian tissues as free dolichol (Free-Dol), fatty acyl d olichyl esters (Dol-FA), and dolichyl phosphate (Dol-P). The hepatic l evel of Dol-P seems to be a rate-limiting factor for glycosylation pro cesses. Previous studies from our laboratory demonstrated the suscepti bility of the dolichol molecule to undergo radical attacks. Since the toxicity of 1,1,2,2-tetrachloroethane (TTCE)is dependent on the free-r adical production during hepatic biotrasformation, it was of interest to determine whether this haloalkane might affect glycosylation mechan isms by changing dolichol levels and distribution in rat liver microso mes and Golgi apparatus (GA). Male Sprague-Dawley rats received a sing le dose of TTCE (574 mg/kg body weight) and were then sacrificed at di fferent times (5, 15, 30, or 60 min). In the TTCE-treated rats both se rum aspartate aminotransferase (AST) and alanine aminotransferase (ALT ) activities and hepatic triglycerides (TG) were significantly higher than control, while microsomal glucose 6-phosphatase (G6Pase) activity was decreased. In total microsomes Dol-P levels considered late-limit ing for the biosynthesis of the N-glycosylated proteins were significa ntly lower than in the control group 15 min after TTCE treatment. In n ormal rat liver, F-1 secretory fraction of CA is 60-fold enriched in t otal dolichol content with respect to microsomes. In this compartment the total dolichol content essential for the increase in membrane flui dity and permeability required for glycoprotein maturation and secreti on, decreased significantly 5 min after TTCE treatment. Our results su ggest that TTCE may affect dolichol functions in rat liver.