Comparison of the skin tumor-initiating activities of dihydrodiols and diol-epoxides of various polycyclic aromatic hydrocarbons.
Comparison of the skin tumor-initiating activities of dihydrodiols and diol-epoxides of various polycyclic aromatic hydrocarbons.
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各种多环芳烃的二氢二醇和二醇环氧化物的皮肤肿瘤引发活性的比较。
作者：
T. Slaga;G. Gleason;G. Mills;L. Ewald;P. Fu;H. Lee;R. Harvey
本文用二阶段致瘤系统测定了二苯并（a，h）蒽、二苯并（a，c）蒽、蒽、7-甲基苯并（a）蒽和苯并（e）芘的二氢二醇和二醇环氧化物诱发小鼠皮肤肿瘤的能力。当局部应用于Sencar小鼠时，发现（±）-反式-3，4-二羟基-3，4-二氢-7-甲基苯并（a）蒽和（±）-反式-1，2-二羟基-1，2-二氢屈比其相应的母体碳氢化合物更具活性，然后每周两次应用12-O-十四烷酰基佛波醇-13-乙酸酯。（±）-反式-9，10-二羟基-9，10-二氢-苯并（e）芘的活性虽高于苯并（e）芘，但并不显著。发现（±）-反式-3，4-二羟基-3，4-二氢二苯并（a，h）蒽的致瘤能力只有二苯并（a，h）蒽的一半。（±）-反式-3，4-二羟基-3，4-二氢蒽和（±）-反式-10，11-二羟基-10，11-二氢二苯并（a，c）蒽作为皮肤肿瘤引发剂基本上是无活性的。反式-9，10-二羟基-反式-11，1,2-环氧-9，10，11，1,2-四氢苯并（e）芘、反式-3，4-二羟基-反式-1，2-环氧-1，2，3，4-四氢二苯并（a，h）蒽、反式-10，11-二羟基-反式-1,2，13-环氧-10，11，1,2，13-四氢二苯并（a，c）蒽和反式-3，4-二羟基-反式-1，2，3，4-四氢二苯并（a，h）蒽，2-环氧-1，2，3，4-四氢-7-甲基苯并蒽也被发现是无活性的肿瘤引发剂。反式-1，2-二羟基-反式-3，4-环氧-1，2，3，4-四氢蝶啶的活性为蝶啶的25%。结果表明，环湾区二醇环氧化物的直接代谢前体7-甲基苯并（a）蒽、二苯并（a，h）蒽和蒽的二氢二醇具有中到高的引发活性，而苯并（e）芘的二氢二醇（一种极弱的引发剂）的活性较弱。海湾地区的二醇-环氧化物的金是唯一的二醇环氧化物测试时，有显着的活动相比，相应的母烃。一些二氢二醇的数据提供了多环烃致癌的海湾区理论的进一步支持。
The abilities of dihydrodiols and diol-epoxides of dibenz( a,h )anthracene, dibenz( a,c )anthracene, chrysene, 7-methylbenz( a )anthracene, and benzo( e )pyrene to initiate skin tumors in mice were determined by using a two-stage system of tumorigenesis. (±)- trans -3,4-Dihydroxy-3,4-dihydro-7-methylbenz( a )anthracene and (±)- trans -1,2-dihydroxy-1,2-dihydrochrysene were found to be more active than their corresponding parent hydrocarbons when applied topically to Sencar mice, followed by twice-weekly applications of 12- O -tetradecanoylphorbol-13-acetate. Although, (±)- trans -9,10-dihydroxy-9,10-dihydro-benzo( e )pyrene had more activity than benzo( e )pyrene, it was not significantly higher. (±)- trans -3,4-Dihydroxy-3,4-di-hydrodibenz( a,h )anthracene was found to have one-half of the tumor-initiating ability of dibenz( a,h )anthracene. (±)- trans -3,4-Dihydroxy-3,4-dihydrochrysene and (±)- trans -10,11-dihydroxy-10,11-dihydrodibenz( a,c )anthracene were essentially inactive as skin tumor initiators. trans -9,10-Dihydroxy- anti -11,12-epoxy-9,10,11,12-tetrahydrobenz( e )pyrene, trans-3,4-dihydroxy-anti-1,2-epoxy-1,2,3,4-tetrahydrodibenz( a,h )anthracene, trans -10,11-dihydroxy- anti -12,13-epoxy-10,11,12,13-tetrahydrodibenz( a,c )anthracene, and trans -3,4-dihydroxy- anti -1,2-epoxy-1,2,3,4-tetrahydro-7-methylbenz( a )anthracene were also found to be inactive as tumor initiators. trans -1,2-Dihydroxy- anti -3,4-epoxy-1,2,3,4-tetrahydrochrysene had 25% of the activity of chrysene. Results show that the dihydrodiols of 7-methylbenz( a )anthracene, dibenz( a,h )anthracene, and chrysene, which are the immediate metabolic precursors of bay-region diol-epoxides, have moderate to high initiating activity, whereas the dihydrodiol of benz( e )pyrene (an extremely weak initiator) has weak activity. The bay-region diol-epoxide of chrysene was the only diolepoxide tested that had significant activity when compared to the corresponding parent hydrocarbon. Some of the dihydrodiol data provide further support for the bay-region theory of polycyclic hydrocarbon carcinogenesis.