Publications Repository

Publications Repository

View item 
  •   Home
  • ICR Divisions
  • Closed Research Teams
  • View item
  • Home
  • ICR Divisions
  • Closed Research Teams
  • View item
JavaScript is disabled for your browser. Some features of this site may not work without it.

Hepatic DNA adduct dosimetry in rats fed tamoxifen: a comparison of methods

Thumbnail
Date
2005-03
ICR Author
Phillips, David Hunter
Hewer, Alan
Author
Schild, LJ
Phillips, DH
Osborne, MR
Hewer, A
Beland, FA
Churchwell, MI
Brown, K
Gaskell, M
Wright, E
Poirier, MC
Show allShow less
Type
Journal Article
Metadata
Show full item record
Abstract
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 P-32-postlabeling with either thin layer (P-32-P-TLC) or liquid chromatography (P-32-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)-alpha-(deoxyguanosin-N-2-yl)-tamoxifen (dG-N-2-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-H-3]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-N-2-TAM varied by 2.5-fold. Ratios of dG-N-2-TAM:(E)-alpha-(deoxyguanosin-N-2-yl)-N-desmethyltamoxifen (dG-N-2-N-desmethyl-TAM) in the second study were similar to 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.
URI
https://repository.icr.ac.uk/handle/internal/2604
DOI
https://doi.org/10.1093/mutage/gei015
Collections
  • Closed Research Teams
Research team
Human Biomonitoring & Carcinogen Activation
Language
eng
License start date
2005-03
Citation
MUTAGENESIS, 2005, 20 pp. 115 - 124
Publisher
OXFORD UNIV PRESS

Browse

All of ICR repositoryICR DivisionsBy issue dateAuthorsTitlesPublication TypesThis collectionBy issue dateAuthorsTitlesPublication Types
  • Login
  • Registered office: The Institute of Cancer Research, 123 Old Brompton Road, London, SW7 3RP
    A Charity, Not for Profit. Company Limited by Guarantee.
    Registered in England No. 534147. VAT Registration No. GB 849 0581 02.