Journal Article

Partial characterization of two major liver I-compounds as unstable adducts which are readily hydrolyzed to unmodified guanine nucleotides.

G D Zhou, S V Vulimiri, E Randerath and K Randerath

in Carcinogenesis

Volume 19, issue 10, pages 1863-1866
Published in print October 1998 | ISSN: 0143-3334
Published online October 1998 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/19.10.1863
Partial characterization of two major liver I-compounds as unstable adducts which are readily hydrolyzed to unmodified guanine nucleotides.

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I-compounds are endogenous bulky DNA modifications which are detected by nuclease P1-enhanced 32P-post-labeling in tissue DNA of animals not knowingly exposed to carcinogens. Their profiles and levels depend inter alia on animal age, species, strain, tissue, gender, diet and exposure to chemicals such as cytochrome P450 inducers and carcinogens. Due to lack of sufficient material obtainable from in vivo sources, chemical structures of I-compounds and their parent normal bases have not yet been identified. In this report we provide 32P-post-labeling and chromatographic evidence that two prominent I-compounds, herein called C1 and C2, which occur at relatively high levels in pig liver DNA are guanine derivatives. This result was obtained by showing that both compounds, isolated from 32P-post-labeling thin-layer maps, were chemically unstable, i.e. they could be readily hydrolyzed to 32P-post-labeled deoxyguanosine 3',5'-bisphosphate by heating in water. C1 appeared particularly labile, undergoing hydrolysis during thin-layer chromatography at pH 3.3 without heating. Several other I-compounds and adducts, as well as the four normal DNA nucleotides, were, however, highly resistant to hydrolysis under the conditions used here. The possible significance of these findings will be briefly discussed.

Journal Article.  0 words. 

Subjects: Clinical Cytogenetics and Molecular Genetics

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