Bond J A
Cancer Res. 1983 Oct;43(10):4805-11.
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.
吸入性环境污染物中发现的许多外源性物质的呼吸道生物转化通常被认为是肺组织对这些外源性物质产生诱变、致癌和/或毒性反应所必需的。典型的环境污染物含有吸附在颗粒上的已知致癌物，这些颗粒可沉积在呼吸道的鼻咽区域。本研究的目的是表征大鼠鼻组织的代谢能力。研究了氧化酶和非氧化酶活性，包括芳烃羟化酶（AHH）、环氧化物水解酶（EH）、尿苷5'-二磷酸葡萄糖醛酸转移酶（UDPGT）和谷胱甘肽转移酶。AHH、EH、UDPGT和谷胱甘肽转移酶的比酶活性分别为每分钟每毫克蛋白质0.023、6.4、20.4和24.8 nmol产物。苯并(a)芘被AHH代谢为二氢二醇、醌和酚，其生成量比大鼠肺微粒体报道的量大约高10倍。在将大鼠鼻组织与苯并(a)芘一起孵育的反应瓶中，还检测到少量但可检测到的苯并(a)芘四醇。通过腹腔注射（苯巴比妥、3-甲基胆蒽、多氯联苯混合物1254和2,3,7,8-四氯二苯并对二恶英）和吸入暴露（苯并(a)芘）用各种诱导剂预处理大鼠，试图提高AHH、EH和UDPGT的微粒体酶活性，结果只有在用2,3,7,8-四氯二苯并对二恶英预处理后大鼠鼻单加氧酶被诱导（2倍）。苯巴比妥使EH和UDPGT的酶活性增加了约50%。这些数据表明大鼠鼻组织可能含有多种形式的细胞色素P-450以及EH和UDPGT。本研究结果支持鼻组织在确定吸入性外源性物质的代谢命运方面可能很重要这一观点。
