Qato M K, Guenthner T M
Department of Pharmacology, University of Illinois College of Medicine at Chicago, 60612.
Toxicol Lett. 1995 Jan;75(1-3):201-7. doi: 10.1016/0378-4274(94)03181-6.
We have used the 32P-postlabeling technique to examine the binding of safrole 2',3'-oxide to DNA. At least 8 covalent adducts are formed when calf thymus DNA is incubated with this oxygenated metabolite of safrole in vitro. However, no corresponding adducts are formed with liver DNA when whole animals are exposed to safrole 2',3'-oxide, or safrole itself. Although safrole 2',3'-oxide is readily formed in vivo, and is sufficiently reactive to covalently bind to DNA, it is probably not a factor in the in vivo genotoxicity of safrole. We also demonstrate that adducts with similar mobility to the major safrole 2',3'-oxide-DNA adduct are formed in vitro between safrole 2',3'-oxide and deoxyguanosine, and also between its chemical analogs allylbenzene 2',3'-oxide or estragole 2',3'-oxide and DNA.
我们已使用³²P后标记技术来检测黄樟素2',3'-氧化物与DNA的结合情况。当小牛胸腺DNA在体外与黄樟素的这种氧化代谢产物一起孵育时，至少会形成8种共价加合物。然而，当全动物暴露于黄樟素2',3'-氧化物或黄樟素本身时，肝脏DNA中不会形成相应的加合物。尽管黄樟素2',3'-氧化物在体内很容易形成，并且具有足够的反应活性与DNA共价结合，但它可能不是黄樟素体内遗传毒性的一个因素。我们还证明，在体外，黄樟素2',3'-氧化物与脱氧鸟苷之间，以及其化学类似物烯丙基苯2',3'-氧化物或草蒿脑2',3'-氧化物与DNA之间会形成与主要黄樟素2',3'-氧化物-DNA加合物迁移率相似的加合物。
