Törnquist S, Wiklund L, Toftgård R
Chem Biol Interact. 1985 Jul;54(2):185-98. doi: 10.1016/s0009-2797(85)80162-9.
Benzo[a]pyrene (B[a]P) adsorbed onto urban air particles (UAP) or in microcrystalline form (MCr) was administered intratracheally to the isolated perfused lung in doses of 100 and 1.5 micrograms. The appearance rate constant calculated for B[a]P release to the perfusate buffer was significantly lower for B[a]P administered adsorbed onto UAP (0.007 +/- 0.002 min-1) compared to the microcrystalline preparation (0.051 +/- 0.030 min-1). A classical two-compartmental model fitted well to the elimination of B[a]P from the perfusate buffer, after administration in solution to the buffer reservoir; C = 24 e-0.05t + 14 e-0.01t (pmol/ml). The concentration of polar metabolites in the perfusion buffer, at the end of experiments was approx. 9-fold higher for lungs administered the microcrystalline preparation compared to UAP at 1.5 microgram doses. At the 100 microgram dose level, the difference between preparations was only 2-fold, the data indicating that enzyme saturation might be important at the high dose level. With regard to the metabolite pattern, adsorption of B[a]P onto urban air particles caused a relative increase in the formation of B[a]P-9,10-dihydrodiol, whereas the relative formation rate for phenols was decreased. The absolute levels of B[a]P metabolites covalently bound to DNA was significantly higher in lungs given the MCr preparation compared to the UAP. When calculated as the amount metabolites bound, in relation to the total amount polar metabolites at the end of perfusion, however, the UAP preparation was significantly more efficient to enhance the production of DNA binding metabolites; 2.62 +/- 0.59 X 10(-5) vs. 1.33 +/- 0.21 X 10(-5) (pmol covalently DNA-bound metabolites/mg DNA/pmol metabolites formed). The results indicate that urban air particles may exert a cocarcinogenic effect with polynuclear aromatic hydrocarbons by increasing the pulmonary residence time for the carcinogenic hydrocarbon and/or alter the metabolite pattern in a way that enhances the covalent binding of metabolites to DNA.
将吸附在城市空气颗粒物（UAP）上或呈微晶形式（MCr）的苯并[a]芘（B[a]P）以100微克和1.5微克的剂量经气管内注入离体灌注肺。与微晶制剂（0.051±0.030分钟-1）相比，注入吸附在UAP上的B[a]P时，计算得出的B[a]P释放到灌注缓冲液中的出现速率常数显著更低（0.007±0.002分钟-1）。在将溶液注入缓冲液储器后，一个经典的二室模型很好地拟合了B[a]P从灌注缓冲液中的消除；C = 24e-0.05t + 14e-0.01t（皮摩尔/毫升）。在实验结束时，微晶制剂给药的肺中灌注缓冲液中极性代谢物的浓度比1.5微克剂量的UAP给药的肺高约9倍。在100微克剂量水平，制剂之间的差异仅为2倍，数据表明在高剂量水平酶饱和可能很重要。关于代谢物模式，B[a]P吸附在城市空气颗粒物上导致B[a]P - 9,10 - 二氢二醇的形成相对增加，而酚类的相对形成速率降低。与UAP相比，给予MCr制剂的肺中与DNA共价结合的B[a]P代谢物的绝对水平显著更高。然而，当计算为灌注结束时结合的代谢物量相对于总极性代谢物量时，UAP制剂在增强DNA结合代谢物的产生方面效率显著更高；2.62±0.59×10-5对1.33±0.21×10-5（皮摩尔共价结合DNA的代谢物/毫克DNA/形成的代谢物皮摩尔）。结果表明，城市空气颗粒物可能通过增加致癌烃在肺中的停留时间和/或以增强代谢物与DNA共价结合的方式改变代谢物模式，与多环芳烃发挥协同致癌作用。
