Gerhard Stöhrer

Oncogenic Purine Derivatives: Evidence for a Possible Proximate Oncogen

Two additional urinary metabolites of the chemical oncogen 3-hydroxyxanthine are now identified as 8-chloroxanthine and 8-methylmercaptoxanthine. Such products are thought to be derived from a reactive intermediate which can be tentatively considered to be a proximate oncogen. Since each of these 8-substituted xanthines has also been obtained in vitro by reactions of 3-acetoxyxanthine with chloride ion or methionine, their production in vivo can be explained as resulting through the metabolic formation of an activated ester with a reactivity similar to that of the chemical model.

Mutagenesis originating in site-specific DNA damage

Covalent monoadducts are the major types of gene damage after exposure to chemical mutagens and carcinogens. These and other damage structures together give rise to the spectrum of mutations that includes base-pair substitutions, insertions and deletions. In this study we introduced the bulky adduct guanine-8-aminofluorene into defined sites on one or both strands of the lactose operator. After insertion into plasmid pBR322 and replication in Escherichia coli COEC40, operator mutants were recognized on 5-bromo,4-chloro,3-indolyl-beta-D-galactoside plates and by hybridization probing. Out of ten randomly selected mutants, nine were single-base deletions and one was a two-base deletion. All mutations were at the site of modification or immediately adjacent to that site. If modifications were placed into both plasmid strands, preventing excision repair, operator mutants comprised close to 100% of operator-containing plasmids.