Microsomal dealkylase

Liver contained 156 (68-563) pg PCB 126/kg FW pronounced liver enlargement lymphoid depletion of spleen 10-fold increase in hepatic microsomal EROD and benzyoxyresorufin-O-dealkylase 5-fold increase in methoxyresorufin-O-dealkylase Liver had 380 pg PCB 126/kg FW with increasing necrosis above effects plus decreased bone growth, decreased spleen weight, and degenerative lesions of thyroid Liver had 1.1 (0.6-4.5) mg PCB 126/kg FW above effects plus decreased body weight, decreased hepatic thiol concentrations, and increased plasma enzyme activities... 

We employed various substrates to check for MFO in two bivalve species, a salt water mussel (Mytilus edulis) and a fresh water clam (Anodonta sp). Cytochrome P-450 was also studied. Organisms were exposed to 100 PPM Venezuelan crude in a stagnant system for up to one month. Enzyme assays were carried out with digestive gland 9000 g homogenates (17) and cytochrome P-450 analysis, with microsomes (21). The hydrocarbon substrates investigated included 1I+C-labelled benzo(a)pyrene, fluorene, anthracene, and naphthalene. The method used for separation of BP metabolites by thin layer radiochromatography has been described (7). The metabolite detection method for the other aromatic hydrocarbons was essentially the same except methylene chloride was used as metabolite extractant as well as TLC developer. Besides the hydrocarbon substrates, we also checked for other MFO reactions, N-dealkylase with C-imipramine (22) and 0-dealkylase with ethoxycoumarin (15). 

Addison, R.F., M.C. Sadler and R.A. Lubet. Absence of hepatic microsomal pentyl- or benzyl-resoruhn O-dealkylase induction in rainbow trout (Salmo gairdneri) treated with phenobarbitone. Biochem. Pharmacol. 36 1183-1184, 1987. 

Riviere, J.L. (1980). T-Ethoxycoumarin O-dealkylase and cytochrome P-450 from grey partridge hepatic and duodenal microsomes. Biochem. Biophys. Res. Commun., 97, 546-9. 

Methanol inhalation (0, 1000, 2500, or 10000 ppm for 6h) potentiated CCI4 hepatotoxicity in Fischer 344 male rats (Allis et al. 1996). Hepatic microsomes showed increased p-nitrophenol hydroxylase activity but no increase in pentoxyreso-rufin-O-dealkylase or ethoxyresorufin-O-deethyl-ase activities. Hepatic antioxidant levels, glutathione levels and glutathione-S-transferase activity in methanol-treated animals were not different from controls. Pre-treatment with allyl sulphone, a specific chemical inhibitor of CYP2E1, abolished the difference in microsomal metabolism between exposed and control animals. 

Hepatic microsomal 7-ethoxyresorufm 0-dealkylase (EROD) activity was determined according to the method of Burke et al 15) using fluorescence spectrophotometer with excitation and emission wavelengths of 530 and 585 nm, respectively. 

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