Carcinogenesis, Vol 19, 1013-1018, Copyright © 1998 by Oxford University Press
H Wei, Q Cai, L Tian and M Lebwohl
We have investigated the effect of tamoxifen (TAM) on endogenous or
ultraviolet radiation (UVR)-induced oxidative damage to macromolecules in
vitro and in vivo. In a system containing calf thymus DNA exposed to a
germicidal UV lamp, both TAM and 4-hydroxytamoxifen (4-OH-TAM) inhibited
UVR-induced the formation of 8-hydroxy-2'-deoxyguanosine (8- OHdG) in DNA
in a dose-dependent manner. At low concentrations, 4-OH- TAM quenched
8-OHdG more potently than TAM. However, the reduction of 8- OHdG by TAM and
4-OH-TAM became similar at a concentration of 10 microM. In contrast,
ascorbic acid had the similar effect to TAM, whereas glutathione exhibited
little effect on UVR-induced 8-OHdG. The order of quenching efficacy was:
4-OH-TAM > TAM approximately = ascorbic acid > glutathione. We have
further determined the effect of TAM on endogenous 8-OHdG formation, lipid
peroxidation, and protein oxidation in the skin of SENCAR mice. Topical
application of 5 micromol TAM significantly reduced the level of 8-OHdG in
mouse epidermis by approximately 27% (P < 0.05). Endogenous lipid
peroxidation and protein oxidation, measured as malondialdehyde (MDA) and
carbonyl groups, were also substantially reduced by topical TAM. Further
study was conducted to evaluate the effect of TAM on UVR-induced 8-OHdG and
MDA in skin of hairless mice. In mice subacutely exposed to low dose (3.4
kJ/m2 x six doses) and high dose (16.8 kJ/m2 x three doses) of UVB
irradiation, TAM significantly blocked the formation of 8-OHdG in mouse
epidermis by 57- 81% and MDA by 37-65%, respectively. Our studies suggest
that reduction of oxidative damages to biological macromolecules in vitro
and in vivo may at least in part explain the anti-carcinogenic and
chemopreventive actions of tamoxifen.
ARTICLES
Tamoxifen reduces endogenous and UV light-induced oxidative damage to DNA, lipid and protein in vitro and in vivo
Department of Dermatology, The Mount Sinai Medical Center, New York, NY 10029, USA. hw@doc.mssm.edu
![]()
CiteULike
Connotea
Del.icio.us What's this?
This article has been cited by other articles:
![]() |
T. K S Ku and D. L Crowe Coactivator-mediated estrogen response in human squamous cell carcinoma lines J. Endocrinol., April 1, 2007; 193(1): 147 - 155. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. M. Balansky, A. Izzotti, F. D'Agostini, A. Camoirano, M. Bagnasco, R. A. Lubet, and S. De Flora Systemic genotoxic effects produced by light, and synergism with cigarette smoke in the respiratory tract of hairless mice Carcinogenesis, September 1, 2003; 24(9): 1525 - 1532. [Abstract] [Full Text] [PDF] |
||||
![]() |
N. R. Bianco, G. Perry, M. A. Smith, D. J. Templeton, and M. M. Montano Functional Implications of Antiestrogen Induction of Quinone Reductase: Inhibition of Estrogen-Induced Deoxyribonucleic Acid Damage Mol. Endocrinol., July 1, 2003; 17(7): 1344 - 1355. [Abstract] [Full Text] [PDF] |
||||
![]() |
M J Campbell, J V Woodside, J Secker-Walker, A Titcomb, and A J C Leathem IGF status is altered by tamoxifen in patients with breast cancer Mol. Pathol., October 1, 2001; 54(5): 307 - 310. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. Duez, M. Hanocq, and J. Dubois Photodynamic DNA damage mediated by {{delta}}-aminolevulinic acid-induced porphyrins Carcinogenesis, May 1, 2001; 22(5): 771 - 778. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. Clarke, F. Leonessa, J. N. Welch, and T. C. Skaar Cellular and Molecular Pharmacology of Antiestrogen Action and Resistance Pharmacol. Rev., March 1, 2001; 53(1): 25 - 72. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. Schiff, P. Reddy, M. Ahotupa, E. Coronado-Heinsohn, M. Grim, S. G. Hilsenbeck, R. Lawrence, S. Deneke, R. Herrera, G. C. Chamness, et al. Oxidative Stress and AP-1 Activity in Tamoxifen-Resistant Breast Tumors In Vivo J Natl Cancer Inst, December 6, 2000; 92(23): 1926 - 1934. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. CARR and B. FREI Does vitamin C act as a pro-oxidant under physiological conditions? FASEB J, June 1, 1999; 13(9): 1007 - 1024. [Abstract] [Full Text] |
||||






