Herreno-Saenz D, Evans F E, Fu P P
National Center for Toxicological Research, Jefferson, Arkansas 72079.
Chem Res Toxicol. 1994 Nov-Dec;7(6):806-14. doi: 10.1021/tx00042a014.
We recently reported that the reaction of N-hydroxy-3-aminobenzo[a] pyrene with calf thymus DNA produced 6-(deoxyguanosin-N2-yl)-3-aminobenzo[a]pyrene as the predominant adduct. The deoxyguanosinyl group of this adduct resides at the C6 position, which is remote from the reaction site, the nitrenium ion. It is significant to determine if formation of this type of DNA adduct is general and whether or not adduct formation is due to an increase in the stabilization of the nitrenium ion by increasing aromaticity. Thus, reduction of 1-nitro-7,8,9,10-tetrahydrobenzo[a]pyrene, 3-nitro-7,8,9,10-tetrahydrobenzo[a]pyrene, and 1-nitrobenzo[a]pyrene, both chemically and enzymatically, followed by reaction with calf thymus DNA was investigated. DNA was isolated and enzymatically digested, and the resulting modified nucleosides were separated by HPLC. Upon spectral analyses by mass and proton nuclear magnetic resonance spectroscopy, 6-(deoxyguanosin-N2-yl)-1-amino-7,8,9,10-tetrahydrobenzo[a] pyrene, 6-(deoxyguanosin-N2-yl)-3-amino-7,8,9,10-tetrahydrobenzo[a]pyrene, and 6-(deoxyguanosin-N2-yl)-1-aminobenzo[a]pyrene were identified, respectively. The same DNA adducts were formed from xanthine oxidase-mediated reductive metabolism of 1-nitro-7,8,9,10-tetrahydrobenzo[a]pyrene, 3-nitro-7,8,9,10-tetrahydrobenzo[a]pyrene, and 1-nitrobenzo[a]pyrene in the presence of calf thymus DNA. Thee results indicate that formation of N2-deoxyguanosinyl adducts of this type is common and that increasing the aromaticity by increasing the number of aromatic rings is not a decisive factor in directing their formation.
我们最近报道，N-羟基-3-氨基苯并[a]芘与小牛胸腺DNA反应产生了6-(脱氧鸟苷-N2-基)-3-氨基苯并[a]芘作为主要加合物。该加合物的脱氧鸟苷基团位于C6位置，远离反应位点氮鎓离子。确定这种类型的DNA加合物的形成是否普遍以及加合物的形成是否是由于通过增加芳香性来提高氮鎓离子的稳定性，这一点很重要。因此，我们研究了1-硝基-7,8,9,10-四氢苯并[a]芘、3-硝基-7,8,9,10-四氢苯并[a]芘和1-硝基苯并[a]芘在化学和酶促作用下的还原反应，随后与小牛胸腺DNA反应。分离DNA并进行酶解，然后通过高效液相色谱法分离得到的修饰核苷。通过质谱和质子核磁共振光谱进行光谱分析后，分别鉴定出了6-(脱氧鸟苷-N2-基)-1-氨基-7,8,9,10-四氢苯并[a]芘、6-(脱氧鸟苷-N2-基)-3-氨基-7,8,9,10-四氢苯并[a]芘和6-(脱氧鸟苷-N2-基)-1-氨基苯并[a]芘。在小牛胸腺DNA存在的情况下，1-硝基-7,8,9,10-四氢苯并[a]芘、3-硝基-7,8,9,10-四氢苯并[a]芘和1-硝基苯并[a]芘经黄嘌呤氧化酶介导的还原代谢也形成了相同的DNA加合物。这些结果表明，这种类型的N2-脱氧鸟苷基加合物的形成是常见的，并且通过增加芳香环的数量来增加芳香性不是指导其形成的决定性因素。
