Rodent Cytochrome

Ethylmorphine and benzphetamine are N-demethylated specifically by rodent cytochrome(s) P-450 (as opposed to cytochrome(s) P] -450) in the rat phenobarbital and the polyhalogenated biphenyls induce these demethylation reactions. However, it is clear that no such stimulation occurred in the rainbow trout (Table II). 

On the other hand, the metabolism of benzo[a]pyrene, ethoxy-coumarin and ethoxyresorufin, which are preferentially oxidized by rodent cytochrome P -450, was greatly induced by the polyhalogenated biphenyls and 3-naphthoflavone. Despite large changes in... 

In summary, it would appear that rainbow trout are responsive to cytochrome P -450-type inducers (e.g. planar polychlorinated biphenyls and polycyclic aromatic hydrocarbons), but are not responsive to cytochrome P-450-type inducers (e.g. phenobar-bital and non-planar polychlorinated biphenyls). Although induced rainbow trout hemoprotein(s) P-450 show high activity with cytochrome P -450 substrates, the induced hemoprotein at 57,000 daltons appears, in electrophoretic and spectral properties, to differ from rodent cytochrome P -450. 

Ubiquinones (coenzymes Q) Q9 and Qi0 are essential cofactors (electron carriers) in the mitochondrial electron transport chain. They play a key role shuttling electrons from NADH and succinate dehydrogenases to the cytochrome b-c1 complex in the inner mitochondrial membrane. Ubiquinones are lipid-soluble compounds containing a redox active quinoid ring and a tail of 50 (Qio) or 45 (Q9) carbon atoms (Figure 29.10). The predominant ubiquinone in humans is Qio while in rodents it is Q9. Ubiquinones are especially abundant in the mitochondrial respiratory chain where their concentration is about 100 times higher than that of other electron carriers. Ubihydroquinone Q10 is also found in LDL where it supposedly exhibits the antioxidant activity (see Chapter 23). 

Tienilic acid- and dihydralazine-induced hepatitis are associated with antibodies against Cyp 2C9 [53] and Cyp 1A2 [54, 55], respectively. These are also the same cytochrome P450s that are responsible for the formation of reactive metabolites of these two drags. Anticonvulsant hepatotoxicity is associated with antibodies against rodent Cyp 3 A and related human enzymes such as thromboxane synthase [56, 57], It is interesting to note that cytochromes P450 are often the target of autoantibodies in idiopathic autoimmune hepatitis [58],... 

CYP1A2, and it also has been shown to be an inducer of CYP1A2 in rodents on account of the increase in hepatic microsomal CYP1A2. Rutaecarpine is an inducer of cytochrome P450(CYP)1A in mouse liver and kidney ". ... 

Kaul, K.L. Novak, R.F. (1987) Inhibition and induction of rabbit liver microsomal cytochrome P-450 by pyridine. J. Pharmacol, exp. Ther., 243, 384-390 Kerckaert, G.A., Brauninger, R., LeBoeuf, R.A. Isfort, R.J. (1996) Use of the Syrian hamster cell transformation assay for carcinogenicity prediction of chemicals currently being tested by the National Toxicology Program in rodent bioassays. Environ. Health Perspect, 104 (Suppl. 5), 1075-1084... 

Thus, fetal liver from primates has a more well-developed metabolic system for xenobiotics than does that from rodents and rabbits, for example. This may be due to the late development of the smooth endoplasmic reticulum and therefore of cytochrome(s) P-450 in the latter species. The use of metabolic inducers and inhibitors in vivo and the use of metabolizing systems with embryo or limb bud culture in vitro have all indicated that for some teratogens,... 

Two dose-dependent alternative pathways involving cytochrome P450 and glutathione -transferases are responsible for the metabolism of dichloromethane in human and rodent cells. 

In rodents and humans, ethylene dibromide is metabolized both by cytochrome P450 and GST enzymes the latter seem to be responsible for DNA adduct formation. In rodents, covalently bound radioactivity has been detected in the epithelial lining of a number of organs. 

DL Busbee Texas A M University Evaluate the induction of cytochrome P-4501A1 in human and animal cells by a series of aromatic and halogenated aromatic hydrocarbons he is also examining whether prior exposure to PAHs significantly alters the amount and type of DNA damage initiated by mutagens in human and rodent cells ... 

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