Carcinogenesis, Vol 19, 1863-1866, Copyright © 1998 by Oxford University Press
GD Zhou, SV Vulimiri, E Randerath and K Randerath
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.
ARTICLES
Partial characterization of two major liver I-compounds as unstable adducts which are readily hydrolyzed to unmodified guanine nucleotides
Department of Pharmacology, Baylor College of Medicine, Houston, TX 77030, USA.
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