Separation of initiating and promoting effects of the skin carcinogen 7-bromomethylbenz(a)anthracene.
Separation of initiating and promoting effects of the skin carcinogen 7-bromomethylbenz(a)anthracene.
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DOI：
10.1093/carcin/1.1.97
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发表时间：
1980
期刊：
影响因子：
4.7
通讯作者：
N. Scribner;J. Scribner
中科院分区：
文献类型：
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作者：
N. Scribner;J. Scribner
二苯并(a,c)蒽和7-溴甲基苯(a)-蒽是具有相当的肿瘤引发能力的碳氢化合物，尽管它们与小鼠皮肤DNA结合的碳氢化合物的量相差约100倍。我们发现它们在鼠伤寒沙门氏菌菌株 TA 100 中具有相当的诱变性，但 7-溴甲基苯并（a）蒽在菌株 TA 1538 和 TA 98 中也具有诱变性。溴化合物也是用 7,12-二甲基苯（a）蒽在小鼠皮肤中引发的肿瘤的强大促进剂，而二苯并（a,c）蒽是作为启动子不活跃。因此，7-溴甲基苯并(a)蒽是小鼠皮肤中有效的完全致癌物，而二苯并(a,c)蒽则不是。这些结果表明，某些类型的化学损伤比其他类型的化学损伤更有效地引发，但广泛的非引发损伤可能更有效地促进。此前已针对不同的烷化剂提出了这一点，这些烷化剂攻击 DNA 和蛋白质的能力不同，但尚未在单一化合物中得到证实。本实验发现7-溴甲基苯并(a)蒽是佛波酯系列之外已知的最强大的皮肤肿瘤促进剂。从这些结果和其他结果可以得出结论，致癌物与 DNA 的总结合与诱变事件或肿瘤起始没有定量相关，但可能是肿瘤发展总体风险的指标。
Dibenz(a,c)anthracene and 7-bromomethylbenz(a)-anthracene are hydrocarbons with comparable tumor initiating potencies, although they differ about 100-fold in the amount of hydrocarbon bound to mouse skin DNA. We have found that they are comparably mutagenic in Salmonella typhimurium strain TA 100, but that 7-bromomethylbenz(a)anthracene is additionally mutagenic in strains TA 1538 and TA 98. The bromo-compound is also a powerful promoter of tumors initiated in mouse skin with 7,12-dimethylbenz(a)anthracene, whereas dibenz-(a,c)anthracene is inactive as a promoter. Accordingly, 7-bromomethylbenz(a)anthracene is an effective complete carcinogen in mouse skin, while dibenz(a,c)anthracene is not. These results suggest that certain types of chemical damage are far more effective than others for initiation, but that extensive non-initiating damage may be effective for promotion. This has previously been proposed for different alkylating agents, which differ in their abilities to attack DNA and protein, but has not been demonstrated in a single compound. 7-Bromomethylbenz(a)anthracene is found in this experiment to be the most powerful skin tumor promoter known outside of the phorbol ester series. It may be concluded from these results and others that total binding of carcinogen to DNA is not quantitatively related to mutagenic events or tumor initiation, but may be an index of overall risk of tumor development.