Bowden G T, McGovern V, Ossanna N, Rosenthal H
Carcinogenesis. 1982;3(5):473-80. doi: 10.1093/carcin/3.5.473.
Vero cells treated with various concentrations of (+/-)7 beta, 8 alpha-dihydroxy-9 alpha, 10 alpha-epoxy, 7,8,9,10-dihydrobenzo[a]pyrene (BP-diol epoxide I) exhibited dose-dependent inhibition in both the rate of DNA synthesis and in the size of nascent DNA. The maximum inhibition was seen 2--3 h after addition of BP-diol epoxide I. A recovery in both the rate of synthesis and size of nascent DNA was observed 5--10 h after treatment. The pH step alkaline elution assay which separates different nascent DNA replication intermediates was used to investigate whether the inhibition and recovery noted above could be accounted for by alterations in DNA replication initiation (DNA synthesis within a replicon) or elongation (rejoining of replicons). At lowest dose studied (0.166 muM BP-diol epoxide I) a reversible inhibition in DNA initiation was observed. At the higher dose levels (0.66 muM and 1.66 muM BP-diol epoxide I) inhibition of both DNA initiation and elongation were observed and inhibition of elongation predominated. The inhibition in elongation was detected by an increase in the relative amount of low molecular weight nascent DNA associated with DNA synthesis within a replicon and a relative decrease in the higher molecular weight elongated DNA. A reversal in the inhibition of both initiation and elongation was noted.
用不同浓度的（±）7β，8α - 二羟基 - 9α，10α - 环氧 - 7,8,9,10 - 二氢苯并[a]芘（BP - 二醇环氧化物I）处理的Vero细胞，在DNA合成速率和新生DNA大小方面均表现出剂量依赖性抑制。在添加BP - 二醇环氧化物I后2 - 3小时观察到最大抑制作用。处理后5 - 10小时观察到新生DNA合成速率和大小均有恢复。采用pH梯度碱性洗脱分析法分离不同的新生DNA复制中间体，以研究上述抑制和恢复是否可归因于DNA复制起始（复制子内的DNA合成）或延伸（复制子的重新连接）的改变。在研究的最低剂量（0.166μM BP - 二醇环氧化物I）下，观察到DNA起始存在可逆抑制。在较高剂量水平（0.66μM和1.66μM BP - 二醇环氧化物I）下，观察到DNA起始和延伸均受到抑制，且延伸抑制占主导。通过与复制子内DNA合成相关的低分子量新生DNA相对量增加和较高分子量延伸DNA相对量减少来检测延伸抑制。同时注意到起始和延伸抑制均有逆转。
