Formation of DNA adducts in human skin maintained in short-term organ culture and treated with coal-tar, creosote or bitumen.

Abstract

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.