Mutagenesis Advance Access published online on March 8, 2005
Mutagenesis, doi:10.1093/mutage/gei015
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1 Carcinogen-DNA Interactions Section, National Cancer Institute, Building 37, Room 4032 NIH, 37 Convent Drive MSC-4255, Bethesda, MD 20892-4255, USA
* To whom correspondence should be addressed. 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)-
Received December 7, 2004
Revised February 4, 2005
Accepted February 7, 2005
Original article
Hepatic DNA adduct dosimetry in rats fed tamoxifen: a comparison of methods
2 Institute of Cancer Research, Brookes Lawley Building, Cotswold Road, Sutton, Surrey, SM2 5NG, UK
3 Division of Biochemical Toxicology, National Center for Toxicological Research, HFT-110, Jefferson, AR 72079, USA
4 Cancer Biomarkers and Prevention Group, The Biocentre, University of Leicester, Leicester LE1 7RH, UK
Miriam C. Poirier, E-mail: poirierm{at}exchange.nih.gov
Abstract 
-(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.
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