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
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.