Study On Prevention Of Estrogen Effect Of Genistein From Irradiation Injury And Its Mechanism

Genistein (Gen) has various effects and activities including anti-oxidation effect, weak estrogenic activity, and anti-cancer activity. Recent researches have shown that Gen can provide protection against ionizing radiation, as show by enhancing 30d survival rate of the mice exposed to radiation damage, reducing the radiation damages to immune systems, and improving peripheral blood cell counts. However, whether there is correlation between the estrogenic activity of Gen and its protective effects against ionizing radiation is still poorly understood. There was a high affinity for ERβand a low affinity for ERαof Gen. In the early studies, Estrogen showed good efficacy in treating acute radiation symptoms, but there was no linear relationship between estrogenic activity and radiation-protective effect. Estrogenic activities were measured through affinities with ERαwhile most radiation sensitive hematopoietic and lymphoid tissue though expressed ERβ. So we hypothesized that the interaction between estrogen and ERβmight be the mechanism through which estrogen provided radiation protection.¹³⁷CS was used as radioactive source and the mice were exposed toγradiation (7.5Gy and 4.0 Gy) once with the whole body to establish the animal model of acute radiation damage. After blocking estrogen receptor activities by Tamoxifen and Faslodex, the influence of Gen on the 30-day survival rate, immune function, genetic transcription, cell cycle accommodation and apoptosis were investigated. The mechanisms through which estrogenic activity of Gen provides protections against ionizing radiation were discussed.Our results showed that: through activating ERβpathway, Gen can(1.) enhance the survival rate of and increase the life span of the radiation exposed mice;(2.) promote regeneration of thymus and spleen, improve the peripheral white blood cells and lymphocytes counts, increase the level of IgA, IgM, and IgG in plasma, and enhance the index of thymus and spleen;(3.) accommodate the cell cycles and reduce occurrence of apoptosis;(4.) inhibit the expression of the proapoptosis gene CD95; increase the expression of DNA repair gene such as urea-DNA glycosylase gene.The aforesaid experimental results suggested that genistein could enhance damage repair and radiation tolerance in mice through activation of estrogen receptorβpathway.