The covalent binding of polycyclic hydrocarbons to DNA in the skin of mice of different strains
The covalent binding of polycyclic hydrocarbons to DNA in the skin of mice of different strains
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多环烃与不同品系小鼠皮肤DNA的共价结合
DOI：
10.1002/ijc.2910220419
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发表时间：
1978
影响因子：
6.4
通讯作者：
P. Sims
中科院分区：
文献类型：
--
作者：
D. Phillips;P. Grover;P. Sims
局部应用碳氢化合物后，在 C57BL、DBA/2 和 Swiss 小鼠中研究了三种氚标记的致癌多环碳氢化合物：7,12-二甲基苯并 (a) 蒽 (DMBA)、苯并 (a) 芘 (BP) 和 3-甲基胆蒽 (MCA) 与小鼠皮肤 DNA 的结合。从处理区域分离的 DNA 被水解为脱氧核糖核苷，并在 Sephadex LH20 柱上进行色谱分析。碳氢化合物与 DNA 的结合水平是根据包含碳氢化合物-DNA 加合物的那些级分中从 Sephadex LH20 柱洗脱的放射性量来确定的，并且通过 AG5OWX4 柱上的重新色谱分析显示的放射性，不包括由于氚掺入正常脱氧核糖核苷而导致的放射性。 C57BL小鼠接受剂量为0.025μmol至1μmol/只的DMBA治疗，并在治疗19小时后测定与DNA结合的碳氢化合物的水平；没有证据表明低于阈值剂量就不会与 DNA 发生结合，并且在所有剂量下都获得了相同的碳氢化合物-DNA 产物峰。在治疗后 6 小时至 8 天期间，比较了 C57BL、DBA/2 和 Swiss 小鼠中 DMBA（1 μmol/小鼠）与皮肤 DNA 的结合水平。 DMBA 在 Swiss 和 C57BL 小鼠中的结合程度相似，在 DBA/2 小鼠中的结合程度稍高；在所有三个菌株中，结合的 DMBA 从 DNA 消失的速度相似。治疗后 19 小时，DMBA（0.1 μmol/小鼠）在 C57BL 和 DBA/2 小鼠中与 DNA 结合的程度相似，而在 Swiss 小鼠中结合程度稍低。碳氢化合物-DNA 产物峰的大小比率随处理后的时间而变化，但对于三个菌株来说在任何给定时间都相似。在所有三种菌株中，处理后 19 小时和 48 小时，BP（1 μmol/小鼠）和 MCA（1 μmol/小鼠）与 DNA 的结合程度相似。处理后19小时，BP（0.1μmol/小鼠）与DNA的结合顺序为DBA/2>C57BL>Swiss。不同菌株中所有三种碳氢化合物的结合水平与所报告的三种菌株对多环烃致癌的敏感性没有相关性。
The binding of three tritium‐labelled carcinogenic polycyclic hydrocarbons, 7,12‐dimethylbenz (a) anthracene (DMBA), benzo (a) pyrene (BP) and 3‐methylcholanthrene (MCA) to DNA in mouse skin has been studied in C57BL, DBA/2 and Swiss mice following topical application of the hydrocarbons. DNA isolated from the treated areas was hydrolysed to deoxyribonucleosides and chromatographed on Sephadex LH20 columns. The levels of binding of hydrocarbon to DNA were determined from the amount of radioactivity eluted from Sephadex LH20 columns in those fractions containing hydrocarbon‐DNA adducts and the radioactivity shown, by rechromatography on AG5OWX4 columns, to be due to tritium incorporation into normal deoxyribonucleosides was not included. C57BL mice were treated with doses of DMBA ranging from 0.025 μmol to 1 μmol/mouse and the levels of hydrocarbon bound to DNA 19 h after treatment were determined; there was no evidence for a threshold dose below which no binding to DNA occurs, and the same hydrocarbon‐DNA product peaks were obtained at all doses. The levels of binding of DMBA (1 μmol/mouse) to DNA in skin were compared in C57BL, DBA/2 and Swiss mice at times varying from 6 h to 8 days after treatment. DMBA became bound to similar extents in Swiss and C57BL mice and to a slightly greater extent in DBA/2 mice; the rate of disappearance of bound DMBA from DNA was similar in all three strains. DMBA (0.1 μmol/mouse) was bound to DNA in C57BL and DBA/2 mice to similar extents 19 h after treatment and to a slightly lesser extent in Swiss mice. The ratios of the sizes of the hydrocarbon‐DNA product peaks varied with the time after treatment, but were similar at any given time for the three strains. Both BP (1 μmol/mouse) and MCA (1 μmol/mouse) were bound to DNA to similar extents 19 h and 48 h after treatment in all three strains. BP (0.1 μmol/mouse) was bound to DNA in the order DBA/2>C57BL> Swiss 19 h after treatment. The levels of binding for all three hydrocarbons in the different strains do not show a correlation with the reported susceptibilities of the three strains to polycylic hydrocarbon carcinogenesis.