Hydroxylase, aryl hydrocarbon

Aryl hydrocarbon hydroxylase (AHH) is part of the microsomal mixed-function oxidase system involved in the detoxification of polycyclic aromatic hydrocarbons. In the HPLC assay developed for the AHH activity, benzo[a]pyrene (BaP) is used as the substrate, and the activity is determined by measuring the unreacted BaP during the reaction. 

The quantitation of BaP was accomplished by reversed-phase HPLC (Li-Chrosorb RP18) with a mobile phase of 10% water in acetonitrile. The column was eluted isocratically, and the BoP was determined with a fluorometer using a 366 nm excitation and monitoring emission at 385 nm. 

SURVEY OF ENZYMATIC ACTIVITIES ASSAYED BY THE HPLC METHOD 

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Ferris IP, LH MacDonald, MA Patrie, MA Martin (1976) Aryl hydrocarbon hydroxylase activity in the fungus Cunninghamella bainierr, evidence for the presence of cytochrome P-450. Arch Biochem Biophys 175 443-452. 

Laboratory studies have reported an excellent correlation between the toxicities of the dibenzo-p-dioxins and related compounds and their abilities to induce aryl hydrocarbon hydroxylase (AHH) activity (Poland and Knutson 1982), suggesting that some mechanistic features may be common to both the toxic and AHH-inducing activities of these compounds. Indeed, both the toxicities and the AHH-inducing activities of the dibenzo-p-diox-ins have found to correlate well with binding affinities to a cytosolic receptor (Poland, Greenlee, and Kende 1979 Poland and Knutson 1982). 

Cheney, B. V. 1982. Structural Factors Affecting Aryl Hydrocarbon Hydroxylase Induction of Dibenzo-p-Dioxins and Dibenzofurans. Int. J. Quant. Chem. 21,445. 

Safe (1984, 1990) described three classes of PCB congeners on the basis of their ability to induce benzo[a]pyrene hydroxylase (also known as aryl hydrocarbon hydroxylase or AHH) and ethoxyresoruhn O-deethylase (EROD) activities ... 

Janz, D.M. and C.D. Metcalfe. 1991a. Relative induction of aryl hydrocarbon hydroxylase by 2,3,7,8-TCDD and two coplanar PCBs in rainbow trout (Oncorhynchus mykiss). Environ. Toxicol. Chem. 10 917-923. 

Ahokas, J.T., O. Pelkonen, and N.T. Karki. 1975. Metabolism of polycyclic hydrocarbons by a highly active aryl hydrocarbon hydroxylase system in the liver of a trout species. Biochem. Biophys. Res. Comm. 63 635-641. 

Herd, J.E. and F.E. Greene. 1980. Effects of perinatal exposure to benzol a Ipyrcnc on the aryl hydrocarbon hydroxylase system of adult rat liver. Biol. Neonate 38 291-299. 

Kiyohara, C., Nakanishi, Y., Inutsuka, S., Takayama, K., Hara, N., Motohiro, A., Tanaka, K., Kono, S. and Hirohata, T. (1998) The relationship between CYP1A1 aryl hydrocarbon hydroxylase activity and lung cancer in a Japanese population. Pharmacogenetics, 8 (4), 315-323. 

Table III. Inhibition of monooxygenase (aryl hydrocarbon hydroxylase) activity in fish and mammalian hepatic microsomes (based on...

Induction of aryl hydrocarbon hydroxylase activity in tele-ost fish (28, 1+1+) and elasmobranch (25.) has also been observed without a hypsochromic shift in the spectrum of the cytochrome P-1+50. CO complex. 

Cytochrome P-U50 in carcinogen metabolism. In spite of the bewildering number of carcinogens involved the important and unifying fact is, that most of the organic carcinogens are not carcinogenic per se, but require metabolic activation in situ by cytochrome P-i 50 mediated aryl hydrocarbon hydroxylase (AHH, also known as BP hydroxylase (EC 1.lU.lit.2)). 

Ahokas, J.T., Pelkonen, 0. and K rki, N.T. The possible role of trout liver aryl hydrocarbon hydroxylase in activating aromatic polycyclic carcinogens. In Jollow, D.J. Kocsis, J.J., Snyder, R. and Vainio, H. (Eds.) Biological Reactive Intermediates. Formation, Toxicity, and inactivation (1977) Plenum Press, New York, pp 162-166. 

Bend, J. R., Hall, P., and Foureman, G. L. Comparison of benzo(a)pyrene hydroxylase (aryl hydrocarbon hydroxylase, AHH) activities in hepatic microsomes from untreated and 1,2,3,4-dibenzanthracene (DBA)-induced little skate (Raja erinacea). Bull. Mt. Desert Island Biol. Lab. (1976) 16. 3-5. 

Concentrations by Hepatic Aryl Hydrocarbon Hydroxylase Activity in the Cunner". M.Sc. Thesis. Memorial Univ. of Newfoundland, St. John s, Nfld., 1978. 

Of additional concern is the thermal conversion of PCBs to polychlorinated dibenzofurans, especially when PCB—filled electrical transformers are involved (16). Further, PCB isomers with no chlorine atoms substituted in the ortho. ortho -biphenvl positions are particularly potent as inducers of aryl hydrocarbon hydroxylase activity. The potency of certain dibenzofurans and non-ortho, ortho chlorine substituted PCBs in inducing activity of these enzymes is similar to that of the highly toxic 2,3,7,8-tetrachloro-dibenzo- -dioxin (15. 17., 18). 

Lin, W.S. and Kapoor, M. Induction of aryl hydrocarbon hydroxylase in Neurospora crassa by benzol a] pyrene, Curr. Microbiol, 3 177-180, 1979. 

AMs are richly endowed with endoplasmic reticulum (ER). Following exposure to cigarette smoke hydrocarbons in the presence of asbestos, the ER synthesizes the enzyme aryl hydrocarbon hydroxylase. This enzyme converts biologically inactive hydrocarbons to metabolically active forms that, when excreted from the cell, react with the extracellular matrix materials. 

No studies were located regarding the metabolic pathway of fuel oils in humans. In one animal study, fuel oil no. 2 applied to the skin of rats induced cutaneous aryl hydrocarbon hydroxylase activity in rat skin microsomal preparations by causing a three-fold induction of benzo(a)pyrene (BaP) 3-hydroxylase activity (Rahimtula et al. 1982). In addition, BaP 3-hydroxylase activity was selectively inhibited by -naphthoflavone, but not by metyrapone, suggesting that cytochrome P-448 enzymes are induced and may participate in the metabolism of this fuel oil (Rahimtula et al. 1982). 

Rahimtula AD, Payne JF, Martins I. 1982. Hydrocarbon-based oils as inducers of cutaneous aryl hydrocarbon hydroxylase. Toxicol Lett 10(2-3) 213-217. 

Aryl hydrocarbon hydroxylase induction. Smoke of cured leaf, administered by inhalation to mice and rats at an undiluted concentration, produced an induction in lungs and kidneys. There was no induction in bowels and liver . 

Lung aryl hydrocarbon hydroxylase activity. Cigarette smoke, administered intranasally to young male C57BL mice fed 5 and 100 ppm of vitamin E, 20 minutes/day for 8 weeks, produced no effect on hepatic aryl hydrocarbon hydroxylase. All of the mice on the vitamin E-free diet showed reduced lung aryl hydrocarbon hydroxylase activity. Lung aryl hydrocarbon hydroxylase activity was increased in all of the smoke-exposed mice L... 

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