TAMOXIFEN REDUCES ENDOGENOUS AND UV LIGHT-INDUCED OXIDATIVE DAMAGE TODNA, LIPID AND PROTEIN IN-VITRO AND IN-VIVO

Citation
Hc. Wei et al., TAMOXIFEN REDUCES ENDOGENOUS AND UV LIGHT-INDUCED OXIDATIVE DAMAGE TODNA, LIPID AND PROTEIN IN-VITRO AND IN-VIVO, Carcinogenesis (New York. Print), 19(6), 1998, pp. 1013-1018
Citations number
41
Categorie Soggetti
Oncology
ISSN journal
01433334
Volume
19
Issue
6
Year of publication
1998
Pages
1013 - 1018
Database
ISI
SICI code
0143-3334(1998)19:6<1013:TREAUL>2.0.ZU;2-4
Abstract
We have investigated the effect of tamoxifen (TAM) on endogenous or ul traviolet radiation (UVR)-induced oxidative damage to macromolecules i n 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) inhi bited UVR-induced the formation of 8-hydroxy-2'-deoxyguanosine (8-OHdG ) in DNA in a dose-dependent manner. At low concentrations, 4-OH-TAM q uenched 8-OHdG more potently than TAM, However, the reduction of 8-OHd G by TAM and COH-TAM became similar at a concentration of 10 mu M. In contrast, ascorbic acid had the similar effect to TAM, whereas glutath ione exhibited little effect on UVR-induced 8-OHdG. The order of quenc hing efficacy was: 4-OH-TAM > TAM approximate to ascorbic acid > gluta thione, We have further determined the effect of TAM on endogenous 8-O HdG formation, lipid peroxidation, and protein oxidation in the skin o f SENCAR mice. Topical application of 5 mu mol TAM significantly reduc ed the level of 8-OHdG in mouse epidermis by similar to 27% (P < 0.05) , Endogenous lipid peroxidation and protein oxidation, measured as mal ondialdehyde (MDA) and carbonyl groups, were also substantially reduce d by topical TAM, Further study was conducted to evaluate the effect o f TAM on UVR-induced 8-OHdG and MDA in skin of hairless mice. In mice subacutely exposed to low dose (3.4 kJ/m(2) x six doses) and high dose (16.8 kJ/m(2) x three doses) of UVB irradiation, TAM significantly bl ocked 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.