Characterization of (+/-)-7,8,10-trihydroxy-7,8,9,10-tetrahydrobenzo[a]pyrene-9-sulfonate.
Characterization of (+/-)-7,8,10-trihydroxy-7,8,9,10-tetrahydrobenzo[a]pyrene-9-sulfonate.
复制标题
(I-)-7,8,10-三羟基-7,8,9,10-四氢苯并[a]芘-9-磺酸盐的表征。
DOI：
10.1021/tx00030a015
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发表时间：
1992
影响因子：
4.1
通讯作者：
Reed,GA
中科院分区：
文献类型：
--
作者：
Green,JL;Reed,GA
某些苯并[a]芘（BP）衍生物在鼠伤寒沙门氏菌菌株中的遗传毒性在添加亚硫酸盐后显著增强。亚硫酸盐与BP衍生物之间的相互作用也导致BP磺酸盐异构体的形成。由于这些三羟基磺酸盐是在BP衍生物和亚硫酸盐的孵育中形成的，其中细菌致突变性发生显着增强，我们研究了这些新的中间体的性质。本文报道了一种新化合物（±）-7，8，10-三羟基-7，8，9，10-四氢苯并[o]芘-9-磺酸盐（BPT-9-sulfonate）的分离和结构鉴定。这种BPT磺酸盐异构体是通过亚硫酸根阴离子自由基与已知前诱变剂（±）-7，8-二羟基-7，8-二氢苯并[o]芘（BP-7，8-diol）的9，10-双键加成而形成的。该加成反应具有自由基性质的证据包括：过氧化物酶催化或化学单电子氧化亚硫酸盐引发反应，酚类抗氧化剂抑制反应，以及链终止产物7，8-二羟基-7，8，9，10-四氢苯并[o]芘-9，10-二磺酸盐（BPD-二磺酸盐）的分离和表征。对S.用BP-7，8-二醇和亚硫酸盐处理鼠伤寒菌株TA 98，其导致回复突变细菌菌落比对照水平增加10倍，表明BPT-9-磺酸盐和BPD-二磺酸盐是仅有的衍生自BP-7，8-二醇的可分离产物。这促使对这些产品的化学性质进行了进一步的研究。发现BPT-9-磺酸盐在水性介质中相当稳定，在3-11的pH范围内对酸或碱催化的水解是难降解的。此外，它是不反应的水性孵育与各种不同的化学和生物亲核试剂的强度。然而，这种BP-三醇磺酸盐能够与纯化的双链小牛胸腺DNA共价结合。实现了335±82 pmol/mg DNA的结合水平，其代表在相同条件下用7 r，8 f-二羟基-9t，10 t-环氧-7，8，9，10-四氢苯并[o]芘获得的水平的约25%。这些数据表明，BPT-9-磺酸盐不是BP-7，8-二醇的末端或无活性解毒产物，而是一种选择性反应中间体，可能在亚硫酸盐介导的苯并[a]芘衍生物活化过程中观察到的遗传毒性增强中发挥作用。
The genotoxicity of certain benzo [a] pyrene (BP) derivatives is significantly enhanced in strains of Salmonella typhimurium following addition of sulfiteto the incubations. The interaction between sulfite and those BP derivatives also results in the formationof isomeric BP sulfonates. As these trihydroxy sulfonates are formed in incubations of BP derivatives and sulfite in which a marked potentiation of bacterial mutagenicity occurs, we have investigated the properties of these novel intermediates. The compound (±)-7, 8, 10-trihydroxy-7, 8, 9, 10-tetrahydrobenzo [o] pyrene-9-sulfonate (BPT-9-sulfonate) was isolated and characterized in terms of its chemical and biologicalactivity. This BPT sulfonate isomer is formedby the addition of the sulfite anion radical to the 9, 10-double bond of the known promutagen,(±)-7, 8-dihydroxy-7, 8-dihydrobenzo [o] pyrene (BP-7, 8-diol). Evidence for the free radical character of this addition includes the initiation of the reaction by either peroxidase-catalyzed or chemical one-electron oxidation of sulfite, the inhibition of the reaction by phenolic antioxidants, and the isolation and characterizationof the chain termination product, 7, 8-dihydroxy-7, 8, 9, 10-tetrahydrobenzo-[o] pyrene-9, 10-disulfonate (BPD-disulfonate). Analysis of incubations of S. typhimurium strain TA98 with BP-7, 8-diol and sulfite, which resulted in a 10-fold increase in revertant bacterial colonies above control levels, showed that BPT-9-sulfonate and BPD-disulfonate were the only isolable products derived from BP-7, 8-diol. This prompted a further investigation of the chemistry of these products. BPT-9-sulfonate was found to be quite stable in aqueous media, being refractory to acid-or base-catalyzed hydrolysis over a pH range of 3-11. Further, it was unreactive in aqueous incubations with a diverse range of chemical and biological nucleophiles of varying strengths. This BP-triol sulfonate was, however, capable of covalent binding to purified, double-stranded calf thymus DNA. Binding levels of 335±82 pmol/mg of DNA were achieved, which represented approximately 25% of the levels obtained with 7r, 8f-dihydroxy-9t, 10t-epoxy-7, 8, 9, 10-tetrahydrobenzo [o] pyrene under identical conditions. Rather than representing a terminal or inactive detoxification product of BP-7, 8-diol, these data suggest that BPT-9-sulfonate is a selectively reactive intermediate which may play a role in the enhanced genotoxicity observed during the sulfite-mediated activation of benzo [a] pyrene derivatives.