Characterization of the benzene monooxygenase system in rabbit bone marrow.
The microsomal fraction of bone marrow contains cytochrome P-450 (39 +/- 11 pmoles/mg microsomal protein) and monooxygenase activity could be demonstrated by the O-dealkylation of 7-ethoxycoumarin (114 +/- 65 pmoles/(min X mg microsomal protein] and the hydroxylation of benzene to phenol (51 +/- 8.6 pmol/45 min X mg microsomal protein). This monooxygenase system differs from that in liver in various aspects. The conversion of benzene to phenol calculated as molecular activity was about 4 times higher than in liver and no induction by phenobarbital could be observed. Aroclor 1254 induced the cytochrome P-450 content about twofold but lowered the O-dealkylation activity of 7-ethoxycoumarin in contrast to liver. Pretreatment with benzene did not change the O-dealkylation in bone marrow, but had a stimulating effect on benzene monooxygenation and covalent binding of 14C-benzene metabolites. From these results we conclude that the bone marrow monooxygenase system develops its own pattern of cytochrome P-450 isoenzymes. Especially after chronic exposure to benzene this system can convert this chemical to phenol and secondary metabolites. The similar behaviour of phenol formation and covalent binding strengthens the hypothesis of a common pathway for metabolism and toxicity but the active intermediate still remains unknown.
D000818:Animals; D001140:Aroclors / Q000494:pharmacology; D001554:Benzene / Q000494:pharmacology; D001853:Bone Marrow / Q000201:enzymology*; D020111:Chlorodiphenyl (54% Chlorine); D004790:Enzyme Induction; D005260:Female; D007700:Kinetics; D008861:Microsomes / Q000187:drug effects / Q000201:enzymology*; D008862:Microsomes, Liver / Q000201:enzymology; D009928:Organ Specificity; D010105:Oxygenases / Q000096:biosynthesis / Q000378:metabolism*; D010634:Phenobarbital / Q000494:pharmacology; D011817:Rabbits
D001140:Aroclors; D020111:Chlorodiphenyl (54% Chlorine); D010105:Oxygenases; C023072:benzene mono-oxygenase; D001554:Benzene; D010634:Phenobarbital