Benzo lipid oxidation

Rats were treated with vehicle (control), phenobarbital (PB), or 3-methylcholanthrene (3-MC). Cytochrome P450, lipid, and reductase fractions were prepared and reconstituted. The reductase and lipid fractions were prepared from PB-treated rats. No hydroxylation activity was detected when hemoprotein was omitted from the reaction mixture. In Experiment 1, benzo[a]pyrene metabolism was measured by formation of fluorescent phenolic metabolites, and benzphetamine metabolism was measured by the rate of benzphetamine-dependent NADPH oxidation. In Experiment 2, the metabolism of pentobarbital, benzo[a]pyrene, and chlorcyclizine was measured by product formation. Experiment 1 was taken from Ref. (53) and Experiment 2 was taken from Ref. (55). 

Ferric oxide has been shown to increase the metabolism of benzo[a]pyrene by hamster alveolar macrophages (Greife and Warshawsky 1993). Alveolar macrophages, the primary lung defense cell, have been shown to metabolize benzo[a]pyrene to a more biologically active from, and then release the metabolites. Concurrent exposure of hamster alveolar macrophages to benzo[a]pyrene-coated ferric oxide resulted in a significant increase in the amount of benzo[a]pyrene metabolites and superoxide anions, which have been shown to produce localized lipid peroxidation and edema in vivo... 

The role of lipid hydroperoxides in activating chemical mutagens is more convincing. A number of studies have demonstrated that lipid hydroperoxides can initiate the free radical oxidation of the carcinogen to the ultimate active form. For example, benzo[Of]pyrene was oxidized to the highly mutagenic 7,8-dihydroxy-9,lO-epoxy-7,8,9,10-... 

Benzo[a]pyrene-3,6-quinol and other quinols are involved in toxic quinone/quinol redox cycles (Lo-RENTZEN and Ts o 1977, Loeentzen etal. 1979). Quinols are formed from the corresponding qui-nones by several reductases. They are rapidly auto-xidizes while superoxide anions are formed. Benzo[fl]pyrene-3,6-quinone has been shown to be mutagenic in the Ames test, using tester strain TA 104 (Chesis et al. 1984) or TA 102, strains which are particularly sensitive to reactive oxygen species. In male Sprague-Dawley rats, a rapid increase of unmetabolised benzo[fl]pyrene was observed in sera 3h after benzo [a] pyrene treatment followed by a sharp decrease (Kim et al. 2000). The time-dependent pattern of serum lipid peroxidation and the level of erythrocyte antioxidant enzymes were shown to be related to the concentrations of the formation of benzo[ ]pyrene-quinones, oxidatively altered lipids and antioxidant enzymes in the blood. 

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