Nordenskjöld M, Jernström B
Chem Biol Interact. 1982 Aug;41(2):155-68. doi: 10.1016/0009-2797(82)90086-2.
Cultured human fibroblasts from healthy donors were incubated for 30 min with nine different benzo[a]pyrene (BP) derivatives in the presence or absence of liver microsomes from 3-methylcholanthrene treated rats. The induction and repair of DNA strand breaks were analysed by alkaline unwinding and separation of double and single stranded DNA (SS-DNA) by hydroxylapatite chromatography immediately after the incubation or at various times after the treatment. In the absence of microsomes DNA stand breaks were detected in fibroblasts exposed to 30 microM of each of the six BP phenols (1-, 2-, 3-, 7-, 9- or 11-OH-BP) and the three BP dihydrodiols (BP-4,5-, BP-7,8- or BP-9,10-dihydrodiol). After removal of the BP derivatives from the medium the DNA strand breaks disappeared within 24 h. alpha-Naphthoflavone (alpha-NF) caused a decrease in the induction of strand breaks by 1-, 3- and 9-OH-BP but did not affect the induction of strand breaks in cells exposed to BP-7,8-dihydrodiol. In the presence of microsomes DNA strand breaks were found after exposure to 30 microM of each of the six BP phenols (1-, 2-, 3-, 7-, 9- or 11-OH-BP), as well as BP-7,8- and 9,10-dihydrodiol. In contrast BP-4,5-dihydrodiol did not induce strand breaks under these conditions. The induction of strand breaks by BP-7,8-dihydrodiol was enhanced in the presence of cytosine-1-beta-D-arabinofuranoside (AraC). In all cases the DNA strand breaks had disappeared 24 h after removal of the BP derivatives and microsomes except after treatment with BP-7,8-dihydrodiol.
将来自健康供体的培养人成纤维细胞与九种不同的苯并[a]芘(BP)衍生物一起孵育30分钟,同时存在或不存在经3-甲基胆蒽处理的大鼠的肝微粒体。孵育后立即或处理后的不同时间,通过碱性解旋以及用羟基磷灰石柱色谱法分离双链和单链DNA(SS-DNA)来分析DNA链断裂的诱导和修复情况。在不存在微粒体的情况下,暴露于六种BP酚(1-、2-、3-、7-、9-或11-OH-BP)以及三种BP二氢二醇(BP-4,5-、BP-7,8-或BP-9,10-二氢二醇)中每一种的30μM的成纤维细胞中检测到DNA链断裂。从培养基中去除BP衍生物后,DNA链断裂在24小时内消失。α-萘黄酮(α-NF)使1-、3-和9-OH-BP诱导的链断裂减少,但不影响暴露于BP-7,8-二氢二醇的细胞中链断裂的诱导。在存在微粒体的情况下,暴露于六种BP酚(1-、2-、3-、7-、9-或11-OH-BP)以及BP-7,8-和9,10-二氢二醇中的每一种的30μM后发现了DNA链断裂。相比之下,BP-4,5-二氢二醇在这些条件下不诱导链断裂。在胞嘧啶-1-β-D-阿拉伯呋喃糖苷(AraC)存在的情况下,BP-7,8-二氢二醇诱导的链断裂增强。在所有情况下,除了用BP-7,8-二氢二醇处理后,去除BP衍生物和微粒体24小时后DNA链断裂都已消失。