Abstract
The mode of binding of a carcinogen, 4-nitroquinoline 1-oxide (4NQO) to DNA was investigated by incubating Ehrlich ascites tumor cells growing in the peritoneal cavity of mice with 14C-labeled 4NQO. DNA extracted from incubated cells had radioactivity associated with DNA after neutral and alkaline cesium chloride equilibrium density-gradient centrifugation. The radioactivity was not released from DNA by heat or alkaline denaturation. Digestion of the 14C-associated DNA by deoxyribonuclease and snake venom phosphodiesterase gave a nucleotide compound which was eluted before ordinary mononucleotides on gel filtration. Phosphomonoesterase treatment of this material yielded a compound which was eluted after mononucleotides on gel filtration and which was not adsorbed on DEAE-cellulose column chromatography. Upon depurination of the 14C-associated DNA under mild conditions, almost all the radioactivity was released with purine bases. The data suggest a covalent binding of 4NQO or its derivatives with purine bases of DNA.
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