Deckers-Schmelzle B, Klaus E, Kahl R, Kahl G F
Naunyn Schmiedebergs Arch Pharmacol. 1978 Jul;303(3):303-7. doi: 10.1007/BF00498059.
The influence of pretreatment with monooxygenase inducers on total irreversible binding of metabolically activated [3H]-benzo(a)pyrene to cellular DNA and the formation of benzo(a)pyrene metabolite-deoxyribonucleoside adducts after cytochrome P-448 induction was studied in perfused rat lungs. Pretreatment with the cytochrome P-448 inducer beta-naphthoflavone increasing binding by a factor of 23. In lungs of induced animals, 0.45 pmoles of benzo(a)pyrene equivalents were bound per mg DNA. Binding to RNA and to protein was also considerably induced by beta-naphthoflavone. Phenobarbital treatment did not significantly increase binding to cellular macromolecules of rat lung. Analysis of hydrolyzed DNA of lungs from beta-naphthoflavone-treated rats by Sephadex LH 20 chromatography revealed the formation of at least two nucleoside adducts with metabolically activated benzo(a)pyrene one of which is probably due to modification of the DNA with a benzo(a)pyrene-7, 8-dihydrodiol-9, 10-epoxide and the other to modification of DNA with secondary metabolites of benzo(a)pyrene phenols.
在灌注的大鼠肺中研究了用单加氧酶诱导剂预处理对代谢活化的[3H] - 苯并(a)芘与细胞DNA的总不可逆结合以及细胞色素P - 448诱导后苯并(a)芘代谢物 - 脱氧核糖核苷加合物形成的影响。用细胞色素P - 448诱导剂β - 萘黄酮预处理使结合增加了23倍。在诱导动物的肺中，每毫克DNA结合0.45皮摩尔苯并(a)芘当量。β - 萘黄酮也显著诱导了与RNA和蛋白质的结合。苯巴比妥处理并未显著增加大鼠肺细胞大分子的结合。通过Sephadex LH 20色谱法分析β - 萘黄酮处理大鼠肺的水解DNA，发现至少形成了两种与代谢活化的苯并(a)芘的核苷加合物，其中一种可能是由于苯并(a)芘 - 7,8 - 二氢二醇 - 9,10 - 环氧化物对DNA的修饰，另一种是由于苯并(a)芘酚的次级代谢物对DNA的修饰。
