Mutagenesis Advance Access originally published online on March 8, 2005
Mutagenesis 2005 20(2):115-124; doi:10.1093/mutage/gei015
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Published by Oxford University Press on behalf of the UK Environmental Mutagen Society 2005
Hepatic DNA adduct dosimetry in rats fed tamoxifen: a comparison of methods
Carcinogen–DNA Interactions Section, National Cancer Institute, Building 37, Room 4032 NIH, 37 Convent Drive MSC-4255, Bethesda, MD 20892-4255, USA, 1Institute of Cancer Research, Brookes Lawley Building, Cotswold Road, Sutton, Surrey, SM2 5NG, UK, 2Division of Biochemical Toxicology, National Center for Toxicological Research, HFT-110, Jefferson, AR 72079, USA and 3Cancer Biomarkers and Prevention Group, The Biocentre, University of Leicester, Leicester LE1 7RH, UK
Liver homogenates from rats fed tamoxifen (TAM) in the diet were shared among four different laboratories. TAM–DNA adducts were assayed by high pressure liquid chromatography–electrospray tandem mass spectrometry (HPLC–ES-MS/MS), TAM–DNA chemiluminescence immunoassay (TAM–DNA CIA), and 32P-postlabeling with either thin layer (32P-P–TLC) or liquid chromatography (32P-P–HPLC) separation. In the first study, rats were fed a diet containing 500 p.p.m. TAM for 2 months, and the values for measurements of the (E)-
-(deoxyguanosin-N2-yl)-tamoxifen (dG-N2-TAM) adduct in replicate rat livers varied by 3.5-fold when quantified using ‘in house’ TAM–DNA standards, or other approaches where appropriate. In the second study, rats were fed 0, 50, 250 or 500 p.p.m. TAM for 2 months, and TAM–DNA values were quantified using both ‘in house’ approaches as well as a newly synthesized [N-methyl-3H]TAM–DNA standard that was shared among all the participating groups. In the second study, the total TAM–DNA adduct values varied by 2-fold, while values for the dG-N2-TAM varied by 2.5-fold. Ratios of dG-N2-TAM:(E)--(deoxyguanosin-N2-yl)-N-desmethyltamoxifen (dG-N2-N-desmethyl-TAM) in the second study were 
1:1 over the range of doses examined. The study demonstrated a remarkably good agreement for TAM–DNA adduct measurements among the diverse methods employed.
* To whom correspondence should be addressed. Tel: +1 301-402-1835; Fax: +1 301-402-8230; Email: poirierm{at}exchange.nih.gov
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