Studies on the role of stimulated epidermal DNA synthesis in the initiation of skin tumors in mice by N-methyl-N'-nitro-N-nitrosoguanidine.
Studies on the role of stimulated epidermal DNA synthesis in the initiation of skin tumors in mice by N-methyl-N'-nitro-N-nitrosoguanidine.
复制标题
N-甲基-N-硝基-N-亚硝基胍刺激表皮 DNA 合成在小鼠皮肤肿瘤引发中的作用研究。
作者：
G. T. Bowden;R. Boutwell
在小鼠皮肤上单次局部涂抹 0.5% 巴豆油，可在涂抹后 18 至 20 小时最大程度地刺激治疗区域的表皮 DNA 合成。在巴豆油预处理后，在最大表皮 DNA 合成时（18 小时）开始使用 N-甲基-N'-硝基-N-亚硝基胍 (MNNG)，然后用巴豆油促进，与用丙酮预处理的一组小鼠相比，随后的肿瘤产量增加了三到四倍。对治疗后不同时间的 MNNG-3H 与整个皮肤和表皮 DNA、RNA 和蛋白质的总结合进行的研究表明，丙酮和巴豆油预处理的小鼠组之间的结合程度没有差异。用丙酮或巴豆油预处理并用MNNG-3H处理的小鼠组的表皮DNA的水解显示出相同的DNA碱基甲基化位置（N -7-鸟嘌呤、O -6-鸟嘌呤和N -3-腺嘌呤）。丙酮和巴豆油预处理组之间这三个 DNA 碱基位置的甲基化程度没有差异。还研究了 MNNG-3H 与复制和非复制表皮 DNA 的结合，在巴豆油预处理组的小鼠中，与复制和非复制 DNA 的结合没有显着差异。刺激表皮 DNA 合成对小鼠皮肤 MNNG 肿瘤发生的影响不能归因于 MNNG-3H 与皮肤 DNA、RNA 或蛋白质结合的增加，也不能归因于表皮 DNA 碱基甲基化的定性或定量差异或 MNNG-3H 与复制表皮 DNA 的优先结合。
A single topical application of 0.5% croton oil to mouse skin stimulates epidermal DNA synthesis in the treated area to a maximum extent 18 to 20 hr after application. Initiation with N -methyl- N ′-nitro- N -nitrosoguanidine (MNNG) after croton oil pretreatment at the time of maximum epidermal DNA synthesis (18 hr) followed by promotion with croton oil caused a three- to fourfold increase in the subsequent tumor yield when compared to a group of mice pretreated with acetone. A study of the total binding of MNNG-3H to whole skin and epidermal DNA, RNA, and protein at various times after treatment showed no difference in the extent of binding between acetone- and croton oil-pretreated groups of mice. Hydrolysis of epidermal DNA from groups of mice pretreated with either acetone or croton oil and treated with MNNG-3H showed the same positions of methylation of DNA bases ( N -7-guanine, O -6-guanine, and N -3-adenine). There was no difference between the acetone- and croton oil-pretreated groups in the extent of methylation of these three DNA base positions. Binding of MNNG-3H to replicating and nonreplicating epidermal DNA was also studied and, in the case of the croton oil-pretreated group of mice, there was no significant difference between the binding to replicating and nonreplicating DNA. The effect of stimulated epidermal DNA synthesis of MNNG tumorigenesis in mouse skin could not be attributed to increased binding of MNNG-3H to skin DNA, RNA, or protein, nor could it be attributed to qualitative or quantitative differences in the methylation of epidermal DNA bases or to preferential binding of MNNG-3H to replicating epidermal DNA.