| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 10902474 | Cancer Letters | 2005 | 9 Pages |
Abstract
Previously, we have identified a set of DHP-derived DNA adducts from DHP-modified calf thymus DNA by 32P-post labeling/HPLC analysis. Metabolism of monocrotaline in the presence of calf thymus DNA resulted in a similar set of DHP-DNA adducts. These DHP-DNA adducts were also found in the liver DNA of rats treated with monocrotaline. The time course of the DHP-derived DNA adduct formation and removal in the liver of rats gavaged with a single dose (10Â mg/kg) of monocrotaline was similar to that of rats treated with riddelliine. The levels of DHP-DNA adducts in liver DNA of rats treated with monocrotaline were much lower than that of riddelliine-treated rats. Results from this study indicate that (i) DHP is a common reactive metabolite for retronecine-type of pyrrolizidine alkaloids, (ii) the formation of DHP-derived DNA adducts in the liver DNA of rats treated with monocrotaline suggests that monocrotaline-induced tumorigenicity is through a genotoxic mechanism.
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Authors
Yu-Ping Wang, Jian Yan, Richard D. Beger, Peter P. Fu, Ming W. Chou,