Effects of vinylidene chloride on DNA synthesis and DNA repair in the rat and mouse: a comparative study with dimethylnitrosamine.
Effects of vinylidene chloride on DNA synthesis and DNA repair in the rat and mouse: a comparative study with dimethylnitrosamine.
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偏二氯乙烯对大鼠和小鼠 DNA 合成和 DNA 修复的影响：与二甲基亚硝胺的比较研究。
DOI：
10.1016/0041-008x(80)90329-4
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发表时间：
1980
影响因子：
3.8
通讯作者：
P. J. Gehring
中科院分区：
文献类型：
--
作者：
R. H. Reitz;P. Watanabe;M. McKenna;J. Quast;P. J. Gehring
据报道，暴露于偏二氯乙烯（VDC）蒸气可诱导小鼠肿瘤，但大鼠显然对VDC的这种影响不敏感。这种物种差异与小鼠更大的激活VDC的能力有关，这种能力可以与大分子反应的反应性亲电试剂。为了增加我们对与这种物种差异相关的分子事件的理解，我们研究了VDC在大鼠和小鼠的肝脏和肾脏中引起DNA烷基化、DNA修复和DNA复制的潜力。为了比较，还研究了强致癌物二甲基亚硝胺（DMN）。雄性Sprague-Dawley大鼠和CD-1小鼠分别暴露于10和50 ppm VDC中6小时。在大鼠和小鼠的肝脏和肾脏中，50 ppm [14C]VDC后的DNA烷基化最小（比报道的大鼠DMN低一到两个数量级）。同样，暴露于50 ppm VDC的小鼠肾脏中的DNA修复仅比对照组高38%，而注射20 mg/kg DMN的小鼠肝脏中的DNA修复则提高了637%。然而，在暴露于50和10 ppm VDC的小鼠肾脏中，发现组织损伤和DNA复制增加（25倍）。在暴露于VDC（50或10 ppm）的小鼠肝脏或暴露于10 ppm VDC的大鼠肝脏或肾脏中未见类似效果。因此，DMN和VDC之间的重要区别已被证明。致瘤剂量的DMN产生相对较小的组织损伤，但与高度的DNA烷基化和DNA修复合成有关。相比之下，暴露于致瘤剂量的VDC导致大量组织损伤，但诱导最小的DNA烷基化或DNA修复合成。这表明，在暴露于VDC的小鼠中观察到的肿瘤主要是通过化学物质对细胞的非遗传成分的影响而产生的。因此，保护人类免受足以造成组织损伤的VDC水平也应有助于防止VDC的任何致癌活性。
Exposure to vinylidene chloride (VDC) vapor has been reported to induce tumors in mice, but rats are apparently insensitive to this effect of VDC. This species difference has been correlated with the greater capacity of mice to activate VDC to a reactive electrophile which can react with macromolecules. To increase our understanding of the molecular events associated with this species difference, we have investigated the potential of VDC to cause DNA alkylation, DNA repair, and DNA replication in the liver and kidneys of rats and mice. For comparative purposes, the potent carcinogen dimethylnitrosamine (DMN) was also studied. Male Sprague-Dawley rats and CD-1 mice were exposed to 10 and 50 ppm VDC for 6 hr. DNA alkylation after 50 ppm [14C]VDC was minimal in liver and kidney of both rats and mice (one or two orders of magnitude less than reported for DMN in rats). Similarly, DNA repair in the kidney of mice exposed to 50 ppm VDC was only 38% higher than control values, while DNA repair in the liver of mice injected with 20 mg/kg DMN was elevated 637%. However, tissue damage and increased DNA replication (25-fold) were seen in the kidneys of mice exposed to 50 and 10 ppm VDC. Comparable effects were not seen in the liver of mice exposed to VDC (50 or 10 ppm) or in the liver or kidneys of rats exposed to 10 ppm VDC. Thus an important distinction between DMN and VDC has been demonstrated. Tumorigenic doses of DMN produced relatively little tissue damage, but were associated with a high degree of DNA alkylation and DNA repair synthesis. In contrast, exposure to tumorigenic doses of VDC resulted in massive tissue damage but induced minimal DNA alkylation or DNA repair synthesis. This suggests that the tumors observed in mice exposed to VDC arise primarily through effects of the chemical on nongenetic components of the cells. Consequently protection of humans from levels of VDC sufficient to cause tissue damage should also serve to preclude any carcinogenic activity of VDC.