Correlation of DNA adduct formation and riddelliine-induced liver tumorigenesis in F344 rats and B6C3F1 mice [Cancer Lett. 193 (2003) 119-125
Riddelliine is a naturally occurring pyrrolizidine alkaloid that induces liver hemangiosarcomas in male and female F344 rats and male B6C3F1 mice. We previously reported that eight dehydroretronecine (DHR)-derived DNA adducts were formed in liver DNA of rats treated with riddelliine. In order to exa...
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Published in | Cancer letters Vol. 207; no. 1; p. 119 |
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Language | English |
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Abstract | Riddelliine is a naturally occurring pyrrolizidine alkaloid that induces liver hemangiosarcomas in male and female F344 rats and male B6C3F1 mice. We previously reported that eight dehydroretronecine (DHR)-derived DNA adducts were formed in liver DNA of rats treated with riddelliine. In order to examine the relationship between DNA adduct levels and the incidence of hemangiosarcomas, we have measured DHR-derived DNA adduct levels in purified rat and mouse liver endothelial cells, the cells of origin for the hemangiosarcomas. F344 rats and B6C3F1 mice were treated by gavage 5 days per week for 2 weeks with riddelliine at 1.0 mg/kg for rats and 3.0 mg/kg for mice. One, 3, 7, and 28 days after the last dose, liver parenchymal and endothelial cell fractions were isolated, and the quantities of DHR-derived DNA adducts were determined by 32P-postlabeling/HPLC. The DHR-derived DNA adduct levels in the endothelial cells were significantly greater than in the parenchymal cells. The DNA adduct levels in rat endothelial cells were greater than in the mouse endothelial cells. These results indicate that the levels of riddelliine-induced DNA adducts in specific populations of liver cells correlate with the preferential induction of liver hemangiosarcomas by riddelliine. |
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AbstractList | Riddelliine is a naturally occurring pyrrolizidine alkaloid that induces liver hemangiosarcomas in male and female F344 rats and male B6C3F1 mice. We previously reported that eight dehydroretronecine (DHR)-derived DNA adducts were formed in liver DNA of rats treated with riddelliine. In order to examine the relationship between DNA adduct levels and the incidence of hemangiosarcomas, we have measured DHR-derived DNA adduct levels in purified rat and mouse liver endothelial cells, the cells of origin for the hemangiosarcomas. F344 rats and B6C3F1 mice were treated by gavage 5 days per week for 2 weeks with riddelliine at 1.0 mg/kg for rats and 3.0 mg/kg for mice. One, 3, 7, and 28 days after the last dose, liver parenchymal and endothelial cell fractions were isolated, and the quantities of DHR-derived DNA adducts were determined by 32P-postlabeling/HPLC. The DHR-derived DNA adduct levels in the endothelial cells were significantly greater than in the parenchymal cells. The DNA adduct levels in rat endothelial cells were greater than in the mouse endothelial cells. These results indicate that the levels of riddelliine-induced DNA adducts in specific populations of liver cells correlate with the preferential induction of liver hemangiosarcomas by riddelliine. |
Author | Yan, Jian Chan, Po-Cheun Fu, Peter P Chou, Ming W Beland, Frederick A Nichols, Jasyl Xia, Qingsu |
Author_xml | – sequence: 1 givenname: Ming W surname: Chou fullname: Chou, Ming W email: mchou@nctr.fda.gov organization: Division of Biochemical Toxicology, National Center for Toxicological Research, Jefferson, AR 72079, USA. mchou@nctr.fda.gov – sequence: 2 givenname: Jian surname: Yan fullname: Yan, Jian – sequence: 3 givenname: Jasyl surname: Nichols fullname: Nichols, Jasyl – sequence: 4 givenname: Qingsu surname: Xia fullname: Xia, Qingsu – sequence: 5 givenname: Frederick A surname: Beland fullname: Beland, Frederick A – sequence: 6 givenname: Po-Cheun surname: Chan fullname: Chan, Po-Cheun – sequence: 7 givenname: Peter P surname: Fu fullname: Fu, Peter P |
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References | 12706867 - Cancer Lett. 2003 Apr 25;193(2):119-25 |
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Snippet | Riddelliine is a naturally occurring pyrrolizidine alkaloid that induces liver hemangiosarcomas in male and female F344 rats and male B6C3F1 mice. We... |
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SubjectTerms | Animals Area Under Curve Carcinogens Cells, Cultured Chromatography, High Pressure Liquid DNA - chemistry DNA - metabolism DNA Adducts Endothelial Cells - drug effects Endothelial Cells - metabolism Female Hemangiosarcoma - chemically induced Liver - cytology Liver - metabolism Liver Neoplasms - chemically induced Liver Neoplasms - genetics Male Mice Models, Chemical Pyrrolizidine Alkaloids - metabolism Pyrrolizidine Alkaloids - pharmacology Rats Rats, Inbred F344 Sex Factors Time Factors |
Title | Correlation of DNA adduct formation and riddelliine-induced liver tumorigenesis in F344 rats and B6C3F1 mice [Cancer Lett. 193 (2003) 119-125 |
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