Some biotransformation enzymes responsible for polycyclic aromatic hydrocarbon metabolism in rat nasal turbinates: effects on enzyme activities of in vitro modifiers and intraperitoneal and inhalation exposure of rats to inducing agents.
Respiratory tract biotransformation of many xenobiotics found in inhaled environmental pollutants is generally considered essential for the mutagenic, carcinogenic, and/or toxic response of lung tissue to these xenobiotics. Typical environmental pollutants contain known carcinogens adsorbed onto particles which can deposit in the nasal pharyngeal region of the respiratory tract. The purpose of this study was to characterize the metabolic capacity of rat nasal tissue. Both oxidative and nonoxidative enzyme activities were investigated which included aryl hydrocarbon hydroxylase (AHH), epoxide hydrolase (EH), uridine 5'-diphosphate-glucuronyltransferase (UDPGT), and glutathione transferase. Specific enzyme activities of AHH, EH, UDPGT, and glutathione transferase were 0.023, 6.4, 20.4, and 24.8 nmol product per mg protein per min, respectively. Benzo(a)pyrene was metabolized by AHH to dihydrodiols, quinones, and phenols in quantities which were about 10 times greater than those reported for rat lung microsomes. Small, but detectable, quantities of benzo(a)pyrene tetrols were also measured in reaction flasks in which rat nasal tissue was incubated with benzo(a)-pyrene. Attempts to increase the microsomal enzyme activities of AHH, EH, and UDPGT by pretreating rats with various inducing agents by both i.p. injection (phenobarbital, 3-methylcholanthrene, Aroclor 1254, and 2,3,7,8-tetrachlorodibenzo-p-dioxine) and inhalation exposure (BaP) resulted in rat nasal monooxygenases only being induced (2-fold) after pretreatment with 2,3,7,8-tetrachlorodibenzo-p-dioxine. Phenobarbital increased enzyme activities of EH and UDPGT by about 50%. These data suggest that rat nasal tissue may contain multiple forms of cytochrome P-450 and of EH and UDPGT. The results from this study support the notion that nasal tissue may be important in determining the metabolic fate of inhaled xenobiotics.
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism; D001564:Benzo(a)pyrene; D001580:Benzopyrenes / Q000494:pharmacology; D001711:Biotransformation; D004851:Epoxide Hydrolases / Q000378:metabolism; D014453:Glucuronosyltransferase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D008297:Male; D009666:Nose / Q000201:enzymology*; D010634:Phenobarbital / Q000494:pharmacology; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology; D011083:Polycyclic Compounds / Q000378:metabolism*; D051381:Rats; D014420:Turbinates / Q000378:metabolism*
D001580:Benzopyrenes; D000072317:Polychlorinated Dibenzodioxins; D011083:Polycyclic Compounds; D001564:Benzo(a)pyrene; D001189:Aryl Hydrocarbon Hydroxylases; D014453:Glucuronosyltransferase; D005982:Glutathione Transferase; D004851:Epoxide Hydrolases; D010634:Phenobarbital