PARTIAL CHARACTERIZATION OF 2 MAJOR LIVER I-COMPOUNDS AS UNSTABLE ADDUCTS WHICH ARE READILY HYDROLYZED TO UNMODIFIED GUANINE-NUCLEOTIDES

I-compounds are endogenous bulky DNA modifications which are detected by nuclease P1-enhanced P-32-post-labeling in tissue DNA of animals no t knowingly exposed to carcinogens, Their profiles and levels depend i nter alia on animal age, species, strain, tissue, gender, diet and exp osure to chemicals such as cytochrome P450 inducers and carcinogens. D ue to lack of sufficient material obtainable from in vivo sources, che mical structures of I-compounds and their parent normal bases have not yet been identified. In this report we provide P-32-post-labeling and chromatographic evidence that two prominent I-compounds, herein calle d C1 and C2, which occur at relatively high levels in pig liver DNA ar e guanine derivatives. This result was obtained by showing that both c ompounds, isolated from P-32-post-labeling thin-layer maps, were chemi cally unstable, i.e. they could be readily hydrolyzed to P-32-post-lab eled deoxyguanosine 3',5'-bisphosphate by heating in water. C1 appeare d particularly labile, undergoing hydrolysis during thin-layer chromat ography at pH 3.3 without heating. Several other I-compounds and adduc ts, as well as the four normal DNA nucleotides, were, however, highly resistant to hydrolysis under the conditions used here. The possible s ignificance of these findings will be briefly discussed.