Source:http://linkedlifedata.com/resource/pubmed/id/11285188
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
4
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| pubmed:dateCreated |
2001-4-4
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| pubmed:abstractText |
It is now generally accepted that activation of tamoxifen occurs as a result of metabolism to alpha-hydroxytamoxifen. In this study, alpha-hydroxytamoxifen was given to female Wistar/Han rats (0.103 or 0.0103 mmol/kg, intraperitoneally, daily for 5 days). This resulted in liver DNA damage, determined by (32)P-post-labelling, of 3333 +/- 795 or 343 +/- 68 adducts/10(8) nucleotides, respectively (mean +/- SD, n = 4). Following HPLC separation, the retention times of the major alpha-hydroxytamoxifen DNA adducts were similar to those seen following the administration of tamoxifen. However, after rats were treated with alpha-hydroxytamoxifen (0.103 mmol/kg) for 5 days and the animals kept for up to 13 months, no liver tumours developed (0/7 rats), even with phenobarbital promotion (0/5 rats). GST-P foci were detected in the liver, but only after 13 months was their number or area significantly increased over the corresponding controls. When alpha-hydroxytamoxifen was given to female lambda/lacI transgenic rats (0.103 mmol/kg orally for 10 days) and the animals killed 46 days later, there was an approximate 1.8-fold increase in mutation frequency but no significant increase in G:C to T:A transversions as described after tamoxifen treatment. It is concluded that DNA damage alone, resulting from the short-term administration of alpha-hydroxytamoxifen, is not sufficient to initiate liver tumours even with phenobarbital promotion. As with tamoxifen, long-term exposure may be required to allow promotion and progression of transformed cells.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Carcinogens,
http://linkedlifedata.com/resource/pubmed/chemical/DNA Adducts,
http://linkedlifedata.com/resource/pubmed/chemical/Glutathione Transferase,
http://linkedlifedata.com/resource/pubmed/chemical/Phenobarbital,
http://linkedlifedata.com/resource/pubmed/chemical/Proliferating Cell Nuclear Antigen,
http://linkedlifedata.com/resource/pubmed/chemical/Tamoxifen,
http://linkedlifedata.com/resource/pubmed/chemical/alpha-hydroxytamoxifen
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| pubmed:status |
MEDLINE
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| pubmed:month |
Apr
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| pubmed:issn |
0143-3334
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:volume |
22
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| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
553-7
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| pubmed:dateRevised |
2003-11-14
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| pubmed:meshHeading |
pubmed-meshheading:11285188-Animals,
pubmed-meshheading:11285188-Animals, Genetically Modified,
pubmed-meshheading:11285188-Carcinogens,
pubmed-meshheading:11285188-Chromatography, High Pressure Liquid,
pubmed-meshheading:11285188-DNA Adducts,
pubmed-meshheading:11285188-DNA Damage,
pubmed-meshheading:11285188-Disease Progression,
pubmed-meshheading:11285188-Female,
pubmed-meshheading:11285188-Glutathione Transferase,
pubmed-meshheading:11285188-Hepatocytes,
pubmed-meshheading:11285188-Liver,
pubmed-meshheading:11285188-Liver Neoplasms,
pubmed-meshheading:11285188-Mutation,
pubmed-meshheading:11285188-Phenobarbital,
pubmed-meshheading:11285188-Proliferating Cell Nuclear Antigen,
pubmed-meshheading:11285188-Rats,
pubmed-meshheading:11285188-Rats, Wistar,
pubmed-meshheading:11285188-Tamoxifen,
pubmed-meshheading:11285188-Time Factors
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| pubmed:year |
2001
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| pubmed:articleTitle |
Short-term dosing of alpha-hydroxytamoxifen results in DNA damage but does not lead to liver tumours in female Wistar/Han rats.
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| pubmed:affiliation |
MRC Toxicology Unit, Hodgkin Building, Lancaster Road, Leicester, LE1 9HN, UK. iw6@le.ac.uk
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| pubmed:publicationType |
Journal Article
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