College of Pharmacy, Department of Pharmaceutical Sciences, University of New Mexico, Albuquerque, New Mexico 87131, USA.
J Toxicol Environ Health A. 2013;76(1):16-24. doi: 10.1080/15287394.2012.722521.
Dibenzo[def,p]chrysene (DBC) is a potent environmental carcinogen in rodents, fish, and human cells examined in culture. There are numerous similarities between the patterns of cytochrome P-450 (P450) activation of DBC and its covalent binding to DNA and proteins with another polycyclic aromatic hydrocarbon (PAH), 7,12-dimethylbenz[a]anthracene (DMBA). Our lab has previously shown that DMBA produces immunosuppression in rodents and human cell systems. Therefore, the purpose of these studies was to examine the immunotoxicity of DBC in a rodent model that was found to be sensitive to the immunosuppressive effects of DMBA. Data showed that DBC had similar potency to DMBA in producing suppression of a T-dependent antibody response (TDAR) and altered spleen cell subsets in a similar manner as DMBA when DMBA was given by gavage for 5 d in corn oil to mice at doses of 1-100 mg/kg total cumulative doses. T-cell-independent antigen (TNP-Ficoll) responses were quantitatively less sensitive to DBC suppression. It was also found that as with DMBA, DBC produced a persistent immunosuppression, which lasted for at least 4 wk following dosing with a novel pill method for self-administration of DBC. In conclusion, DBC appears to possess many of the same characteristics of DMBA in terms of its immunotoxicity.
二苯并[a,h]蒽(DBC)是一种在啮齿动物、鱼类和培养的人类细胞中具有很强致癌性的环境污染物。DBC 对细胞色素 P-450(P450)的激活模式及其与另一种多环芳烃(PAH)7,12-二甲基苯并蒽(DMBA)的 DNA 和蛋白质的共价结合与 DMBA 有许多相似之处。我们实验室之前已经表明,DMBA 在啮齿动物和人类细胞系统中会产生免疫抑制作用。因此,这些研究的目的是在一种对 DMBA 的免疫抑制作用敏感的啮齿动物模型中研究 DBC 的免疫毒性。数据表明,DBC 产生 T 依赖性抗体反应(TDAR)抑制和脾细胞亚群改变的效力与 DMBA 相似,当 DMBA 在玉米油中通过灌胃给予小鼠时,总累积剂量为 1-100mg/kg,连续 5 天。T 细胞非依赖性抗原(TNP-Ficoll)反应对 DBC 抑制的敏感性较低。还发现,与 DMBA 一样,DBC 产生了持续的免疫抑制,在通过新的药丸方法给予 DBC 进行自我给药后至少 4 周内持续存在。总之,DBC 在免疫毒性方面似乎具有与 DMBA 相同的许多特征。