Kurelec B, Krca S, Garg A, Gupta R C
Center for Marine Research Zagreb, Ruder Bosković Institute, Croatia, Yugoslavia.
Cancer Lett. 1991 May 24;57(3):255-60. doi: 10.1016/0304-3835(91)90165-e.
We have investigated the formation of DNA adducts in starved, fed and 5,6-benzoflavone-pretreated carp following i.p. administration of benzo(a)pyrene. 32P-postlabeling analysis of the liver DNAs showed the presence of one predominant (greater than 92%) adduct in all three groups. Cochromatography experiments revealed that the main adduct was identical to authentic BPDEI-dG (10 beta-(deoxyguanosin-N2-yl)-7 beta, 8 alpha, 9 alpha-trihydroxy-7,8,9,10-tetrahydrobenzo[a]pyrene). The formation of the adduct was evident as early as 1.5 h post-treatment and the levels increased steadily up to 7 days, reaching about 125, 110 and 102 attomole/microgram DNA in starved, fed and benzoflavone-pretreated carp, respectively. During this period, the benzo[a]pyrene-induced benzo[a]-pyrene monooxygenase activity increased from the uninduced, natural level of about 3 pmol/mg per min to levels of 35, 62 and 79 pmol/mg per min in starving, fed and 5,6-benzoflavone pretreated fish, respectively. A slow but steady formation of the diolepoxide-dG adduct was also observed in the liver DNA of carp following p.o. treatment. These results indicate that carp can biotransform polycyclic aromatic hydrocarbons such as benzo[a]pyrene to 'reactive' metabolites that bind to DNA.
我们研究了腹腔注射苯并(a)芘后,饥饿、喂食以及经5,6 - 苯并黄酮预处理的鲤鱼体内DNA加合物的形成情况。对肝脏DNA进行的32P后标记分析表明,所有三组中均存在一种主要的(大于92%)加合物。共色谱实验显示,主要加合物与 authentic BPDEI - dG(10β - (脱氧鸟苷 - N2 - 基) - 7β, 8α, 9α - 三羟基 - 7,8,9,10 - 四氢苯并[a]芘)相同。加合物的形成早在处理后1.5小时就很明显,其水平在7天内稳步上升,在饥饿、喂食和经苯并黄酮预处理的鲤鱼中,分别达到约125、110和102阿托摩尔/微克DNA。在此期间,苯并[a]芘诱导的苯并[a]芘单加氧酶活性从未诱导的天然水平约3皮摩尔/毫克每分钟分别增加到饥饿、喂食和经5,6 - 苯并黄酮预处理的鱼中的35、62和79皮摩尔/毫克每分钟。经口服处理后,在鲤鱼肝脏DNA中也观察到二环氧物 - dG加合物的缓慢但稳定的形成。这些结果表明,鲤鱼能够将多环芳烃如苯并[a]芘生物转化为与DNA结合的“活性”代谢物。