Abstract

When S-(1,2-dichlorovinyl)- l-cysteine is cleaved by a lyase in vitro, a very reactive alkylating fragment (AF) is produced which can combine with a variety of acceptors, including DNA. Using 35S as tracer of AF, it was shown that histone, added as such, and particularly in the form of bovine thymus chromatin reacted with AF and greatly decreased the extent to which AF combined with DNA. In contrast to DNA treated directly with AF, DNA which was isolated from AF-treated chromatin retained most of its primer activity for DNA and RNA polymerases and its susceptibility to hydrolysis by pancreatic DNase I. These results illustrate the role which histones and perhaps other nuclear proteins may have in protecting DNA against interaction with various toxic agents. They may also have a bearing on the susceptibility of various cells, tissues and species to the effects of proximate carcinogens and other proximate toxicants formed by metabolic reactions of toxic or therapeutic agents in vivo.

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