Li K M, Todorovic R, Rogan E G, Cavalieri E L, Ariese F, Suh M, Jankowiak R, Small G J
Eppley Institute for Research in Cancer, University of Nebraska Medical Center, Omaha 68198-6805, USA.
Biochemistry. 1995 Jun 27;34(25):8043-9. doi: 10.1021/bi00025a010.
Dibenzo[a,l]pyrene (DB[a,l]P) is the most potent carcinogen known among aromatic hydrocarbons. DB[a,l]P-11,12-dihydrodiol, precursor to the bay-region diol epoxide, is slightly less carcinogenic than the parent compound. DB[a,l]P and its 11,12-dihydrodiol were covalently bound to DNA by cytochrome P-450 in 3-methylcholanthrene-induced rat liver microsomes, and DB[a,l]P was also bound to DNA by horseradish peroxidase. The "stable" (remaining intact in DNA under normal conditions of purification) and "depurinating" (released from DNA by cleavage of the glycosidic link between the purine base and deoxyribose) adducts were identified and quantified. Stable adducts were analyzed by the 32P-postlabeling technique. Depurinating adducts were identified by comparison of their retention times with those of standard adducts on HPLC in two solvent systems. Confirmation of their identity was obtained by means of fluorescence line-narrowing spectroscopy. When DB[a,l]P was activated by horseradish peroxidase, the depurinating adducts 3-(DB[a,l]P-10-yl)adenine (DB[a,l]P-10-N3Ade, 33%), 7-(DB[a,l]P-10-yl)adenine (DB[a,l]P-10-N7Ade, 27%), and 7-DB[a,l]P-10-yl)guanine (DB[a,l]P-10-N7Gua, 5%) were formed. Unidentified stable adducts comprised the remaining 35% of the detected adducts. When DB[a,l]P was activated by microsomes, the one-electron oxidation depurinating adducts DB[a,l]P-10-N3Ade (28%), DB[a,l]P-10-N7Ade (14%), DB[a,l]P-10-N7Gua (2%), and DB[a,l]P-10-C8Gua (6%), as well as the diol epoxide depurinating adducts (+/-)-syn-DB[a,l]P-diol epoxide (DE)-14-N7Ade (31%) and (+/-)-anti-DB[a,l]PDE-14-N7Gua (3%), were formed. Stable adducts predominantly formed via the DB[a,l]PDE pathway represented 16% of the adducts detected.(ABSTRACT TRUNCATED AT 250 WORDS)
二苯并[a,l]芘（DB[a,l]P）是已知的芳烃中致癌性最强的物质。DB[a,l]P - 11,12 - 二氢二醇是湾区二醇环氧化物的前体，其致癌性略低于母体化合物。DB[a,l]P及其11,12 - 二氢二醇在3 - 甲基胆蒽诱导的大鼠肝微粒体中通过细胞色素P - 450与DNA共价结合，DB[a,l]P也通过辣根过氧化物酶与DNA结合。对“稳定”（在正常纯化条件下在DNA中保持完整）和“脱嘌呤”（通过嘌呤碱基与脱氧核糖之间的糖苷键断裂从DNA中释放）加合物进行了鉴定和定量。稳定加合物通过32P后标记技术进行分析。脱嘌呤加合物通过在两种溶剂系统中在高效液相色谱（HPLC）上与标准加合物的保留时间比较来鉴定。通过荧光线窄化光谱法确认其身份。当DB[a,l]P被辣根过氧化物酶激活时，形成了脱嘌呤加合物3 - （DB[a,l]P - 10 - 基）腺嘌呤（DB[a,l]P - 10 - N3Ade，33%）、7 - （DB[a,l]P - 10 - 基）腺嘌呤（DB[a,l]P - 10 - N7Ade，27%）和7 - （DB[a,l]P - 10 - 基）鸟嘌呤（DB[a,l]P - 10 - N7Gua，5%）。未鉴定的稳定加合物占检测到的加合物的其余35%。当DB[a,l]P被微粒体激活时，形成了单电子氧化脱嘌呤加合物DB[a,l]P - 10 - N3Ade（28%）、DB[a,l]P - 10 - N7Ade（14%）、DB[a,l]P - 10 - N7Gua（2%）和DB[a,l]P - 10 - C8Gua（6%），以及二醇环氧化物脱嘌呤加合物（±） - 顺式 - DB[a,l]P - 二醇环氧化物（DE） - 14 - N7Ade（31%）和（±） - 反式 - DB[a,l]PDE - 14 - N7Gua（3%）。主要通过DB[a,l]PDE途径形成的稳定加合物占检测到的加合物的16%。（摘要截短至250字）
