Schoket B, Hewer A, Grover P L, Phillips D H
Chester Beatty Laboratories, Institute of Cancer Research, London, UK.
Int J Cancer. 1988 Oct 15;42(4):622-6. doi: 10.1002/ijc.2910420425.
Adult and foetal human skin samples maintained in short-term organ culture were treated topically with solutions of coal-tar, creosote or bitumen, then DNA was isolated and analysed by 32P-post-labelling for the presence of aromatic DNA adducts. Autoradiographs of the 32P-labelled adducts resolved on polyethyleneimine-cellulose tlc sheets revealed a band of radioactivity indicative of the formation of adducts by a large number of components in these complex carcinogenic mixtures. Single doses of the materials, similar to those used to initiate tumours in experimental animals, resulted in the formation of approximately 0.3 fmol total adducts/micrograms DNA. The levels of adducts formed in human skin are thus similar to those formed in mouse skin after administration of doses known to be carcinogenic to the latter. The results provide direct evidence of DNA damage in human skin by materials strongly suspected of being carcinogenic to humans, and point to a method for evaluating other complex mixtures of aromatic chemicals for their potential carcinogenic hazard.
将成人和胎儿的人类皮肤样本置于短期器官培养中，然后用煤焦油、杂酚油或沥青溶液进行局部处理，接着分离DNA，并通过³²P后标记法分析是否存在芳香族DNA加合物。在聚乙烯亚胺 - 纤维素薄层层析板上解析的³²P标记加合物的放射自显影片显示出一条放射性带，表明这些复杂致癌混合物中的大量成分形成了加合物。与用于在实验动物中引发肿瘤的剂量相似的单剂量材料，导致每微克DNA形成约0.3飞摩尔的总加合物。因此，人类皮肤中形成的加合物水平与已知对小鼠皮肤致癌的剂量给药后在小鼠皮肤中形成的加合物水平相似。这些结果提供了直接证据，证明强烈怀疑对人类致癌的物质会对人类皮肤造成DNA损伤，并指出了一种评估其他芳香族化学物质复杂混合物潜在致癌危害的方法。
