Effect of sulfite on the covalent reaction of benzo[a]pyrene metabolites with DNA.
Effect of sulfite on the covalent reaction of benzo[a]pyrene metabolites with DNA.
复制标题
DOI：
10.1093/carcin/10.2.259
复制
发表时间：
1989-02
期刊：
影响因子：
4.7
通讯作者：
K. H. Leung;D. Keller;D. Menzel
中科院分区：
文献类型：
--
作者：
K. H. Leung;D. Keller;D. Menzel
二氧化硫（SO2）增强了多环芳烃的致癌性。为探讨SO2共致癌机制，测定了SO2水合态亚硫酸盐对苯并[a]芘（BaP）代谢物与DNA体外共价反应的影响。[14C]BaP用大鼠肺或肝脏线粒体后上清（S9）、NADPH生成系统、小牛胸腺DNA和亚硫酸钠（0-20 mM）孵育。在肺S9存在的情况下，随着亚硫酸盐浓度的增加，共价反应从每mg DNA 0.66至1.20 pmol BaP代谢物线性增加。在大鼠肝脏S9中添加亚硫酸盐也增加了BaP-DNA加合物的形成，BaP-DNA加合物从每mg DNA 80 pmol增加到120 pmol。亚硫酸盐改变了肺或肝酶制剂形成的BaP代谢物的数量和模式。随着亚硫酸盐的存在，BaP代谢更广泛，形成的水溶性BaP代谢物数量显著增加。随着肺S9的增加，bap -四醇、二醇和酚的含量略有增加。在肝脏S9中，二醇和苯酚的生成量显著降低，而四醇的生成量不变。大鼠肺S9与亚硫酸盐孵育可形成谷胱甘肽s -磺酸盐（GSSO3H），这是一种已知的谷胱甘肽s -转移酶抑制剂，可介导谷胱甘肽（GSH）和BaP的结合。我们的研究结果表明，亚硫酸盐可能通过改变BaP的整体代谢激活和解毒，或直接与DNA反应，随后影响BaP代谢产物与DNA的共价反应。这些可能的机制可以解释二氧化硫的共致癌作用。
Sulfur dioxide (SO2) potentiates the carcinogenicity of polycyclic aromatic hydrocarbons. To investigate the mechanism of SO2 cocarcinogenesis, the effect of sulfite, the hydrated form of SO2, on the covalent reaction of benzo[a]pyrene (BaP) metabolites with DNA in vitro was measured. [14C]BaP was incubated with rat lung or liver post-mitochondrial supernatant (S9), an NADPH generating system, calf thymus DNA and sodium sulfite (0-20 mM). In the presence of lung S9, covalent reaction increased linearly from 0.66 to 1.20 pmol BaP metabolites per mg DNA with increasing sulfite concentrations. Addition of sulfite to rat liver S9 also increased BaP-DNA adduct formation with BaP-DNA adducts increasing from 80 to 120 pmol per mg DNA. Sulfite altered the amount and pattern of BaP metabolites formed by either lung or liver enzyme preparations. BaP was metabolized more extensively and the amount of water soluble BaP metabolites formed increased significantly with sulfite present. With lung S9, the amount of BaP-tetrols, diols, and phenols increased slightly. With liver S9, diol and phenol formation was significantly lower while tetrol formation was unchanged. Incubation of rat lung S9 with sulfite resulted in formation of glutathione S-sulfonate (GSSO3H), a known inhibitor of glutathione S-transferases mediating the conjugation of glutathione (GSH) and BaP epoxides. Our results suggest that sulfite may, by altering the overall metabolic activation and detoxication of BaP, or by reacting directly with DNA, subsequently affect the covalent reaction of BaP metabolites with DNA. These are offered as possible mechanisms to explain the cocarcinogenic effect of SO2.