Enzymatic activation of the oncogen 3-hydroxyxanthine.

Abstract

The oncogen 3-hydroxyxanthine is enzymatically converted to a chemically reactive form by a protein fraction of the 100,000 × g supernatant of rat liver. The activated derivative reacts in vitro with free or protein-bound methionine, and the assay of the activation is based on the amount of 8-methylmercaptoxanthine formed; 3-hydroxyguanine yields 8-methylmercaptoguanine in this system. The cofactor requirements suggest that the activated intermediate is the 3- O -ester derived from 3-hydroxyxanthine and sulfuric acid. With cofactors favoring phosphate transfer, extensive activation is observed, but the participation of catalytic amounts of sulfate could not be excluded. Experiments with glucuronate or acetate transferring systems were inconclusive. 8-Methylmercaptoxanthine is not altered by the enzyme preparation, although the intact rat metabolized about 10% of it to a product which may be 8-methylsulfinylxanthine.