King L C, Lewtas J
Health Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711.
Toxicol Appl Pharmacol. 1993 Sep;122(1):149-58. doi: 10.1006/taap.1993.1182.
The comparative metabolism of 1-nitropyrene was studied in isolated rabbit, rat, and hamster tracheal epithelial cells commonly used in neoplastic transformation assays. The maximum total metabolite production for all species was attained at 2.0 x 10(6) cells and 4 hr incubation, with no significant increase after 20 hr. The majority of the metabolites produced by tracheal epithelial cells from each species were released into the surrounding medium. The metabolites retained by tracheal epithelial cells were qualitatively identical to those identified in the medium but were present at lower concentrations. The apparent Km for the metabolism of 1-nitropyrene by tracheal epithelial cells was in the order of rabbit (5.1 microM) < hamster (9.1 microM) < rat (13 microM). The apparent V/K value for the metabolism of 1-nitro-pyrene by tracheal epithelial cells was also in the order of rabbit (2.0 nmol/hr/mg protein) > hamster (1.6 nmol/hr/mg protein) > rat (0.48 nmol/hr/mg protein). Intrinsic clearance of the previously characterized mutagenic metabolites (3-OH-1-NAAP, K-DHD, 10-OH-1-NP, 1-AMP, and phenols 6- or 8-OH-1-NP) produced by tracheal epithelial cells at their approximate Km values also indicated that rabbit tracheal cells were more active in the production of these metabolites than either hamster or rat tracheal cells. Although the metabolism of 1-NP in isolated tracheal epithelial cells of these three species was qualitatively similar, rabbit tracheal cells are the most active in metabolizing 1-NP. These results are consistent with the possibility that tracheal epithelial cells may be a target tissue for NO2-PAHs carcinogenesis.
在肿瘤转化试验中常用的分离兔、大鼠和仓鼠气管上皮细胞中研究了1-硝基芘的比较代谢。所有物种在2.0×10⁶个细胞和4小时孵育时达到最大总代谢产物产量，20小时后无显著增加。每个物种的气管上皮细胞产生的大多数代谢产物释放到周围培养基中。气管上皮细胞保留的代谢产物在质量上与培养基中鉴定的代谢产物相同，但浓度较低。气管上皮细胞代谢1-硝基芘的表观Km顺序为兔（5.1微摩尔）＜仓鼠（9.1微摩尔）＜大鼠（13微摩尔）。气管上皮细胞代谢1-硝基芘的表观V/K值顺序也为兔（2.0纳摩尔/小时/毫克蛋白质）＞仓鼠（1.6纳摩尔/小时/毫克蛋白质）＞大鼠（0.48纳摩尔/小时/毫克蛋白质）。气管上皮细胞在其近似Km值下产生的先前表征的诱变代谢产物（3-OH-1-NAAP、K-DHD、10-OH-1-NP、1-AMP和酚类6-或8-OH-1-NP）的内在清除率也表明，兔气管细胞在产生这些代谢产物方面比仓鼠或大鼠气管细胞更活跃。尽管这三种物种的分离气管上皮细胞中1-NP的代谢在质量上相似，但兔气管细胞在代谢1-NP方面最活跃。这些结果与气管上皮细胞可能是NO₂-PAHs致癌作用的靶组织这一可能性一致。
