Guo T L, Zhang X L, Bartolucci E, McCay J A, White K L, You L
Department of Pharmacology and Toxicology, Virginia Commonwealth University, P.O. Box 980613, Richmond, VA 23298-0613, USA.
Toxicology. 2002 Apr 2;172(3):205-15. doi: 10.1016/s0300-483x(02)00005-7.
The isoflavone genistein (GE) and methoxychlor (MXC) have been shown to be estrogenic in both in vitro and in vivo experimental systems. The objective of the present study was to evaluate the effects of GE and MXC on the immune system in adult and developing rats and the potential interaction between these compounds in their immunomodulatory actions. Timely pregnant Sprague-Dawley rats were exposed to GE (300 or 800 ppm), MXC (800 ppm), or their combinations in feed starting on day 1 of gestation. The offspring were exposed to these chemicals gestationally and lactationally. Immunological evaluation was performed on postnatal day 22. In F0 females, exposure to GE had no effect on the percentages of thymocyte subsets, but caused a significant decrease in the absolute thymus weight at the 800-ppm dose level. In the spleen, GE did not affect the activity of natural killer cells but induced changes in the percentages of splenic T lymphocyte subsets. Exposure to MXC produced no effect on the immune parameters examined except for a decrease in the percentage of CD4+CD8- thymocytes. Additionally, minimal interaction between GE and MXC was observed. In F(1) males, both GE and MXC decreased the percentage of CD4+CD8- thymocytes, but only GE increased spleen natural killer cell activity. MXC in combination with 300 ppm-GE, but not separately, produced significant decreases in the absolute weights of thymus and spleen. In F1 females, GE decreased the percentage of CD4+CD8- thymocytes, increased the percentage of CD4+CD8+ thymocytes, and decreased the activity of spleen natural killer cells. In contrast, MXC increased the percentages of spleen natural killer cells and CD8+ T cells. Overall, the results demonstrate that both GE and MXC can modulate the immune system with greater effects observed in developing rats. Moreover, male and female rats have differential responses to these compounds. A lack of interaction between these two estrogenic chemicals in modulating these immune parameters indicates that their effects on the immune system might involve other mechanisms in addition to the estrogen receptors.
异黄酮染料木黄酮（GE）和甲氧滴滴涕（MXC）已在体外和体内实验系统中均显示出雌激素活性。本研究的目的是评估GE和MXC对成年及发育中大鼠免疫系统的影响，以及这些化合物在免疫调节作用中的潜在相互作用。将处于孕期的Sprague-Dawley大鼠从妊娠第1天开始在饲料中分别给予GE（300或800 ppm）、MXC（800 ppm）或它们的组合。子代在妊娠期和哺乳期均接触这些化学物质。在出生后第22天进行免疫评估。在F0代雌性大鼠中，接触GE对胸腺细胞亚群的百分比没有影响，但在剂量为800 ppm时导致绝对胸腺重量显著降低。在脾脏中，GE不影响自然杀伤细胞的活性，但诱导脾脏T淋巴细胞亚群百分比发生变化。接触MXC除了使CD4 + CD8 - 胸腺细胞百分比降低外，对所检测的免疫参数没有影响。此外，观察到GE和MXC之间的相互作用极小。在F1代雄性大鼠中，GE和MXC均降低了CD4 + CD8 - 胸腺细胞的百分比，但只有GE增加了脾脏自然杀伤细胞的活性。MXC与300 ppm的GE联合使用（而非单独使用）可使胸腺和脾脏的绝对重量显著降低。在F1代雌性大鼠中，GE降低了CD4 + CD8 - 胸腺细胞的百分比，增加了CD4 + CD8 + 胸腺细胞的百分比，并降低了脾脏自然杀伤细胞的活性。相比之下，MXC增加了脾脏自然杀伤细胞和CD8 + T细胞的百分比。总体而言，结果表明GE和MXC均可调节免疫系统，且在发育中的大鼠中观察到的影响更大。此外，雄性和雌性大鼠对这些化合物有不同的反应。这两种雌激素类化学物质在调节这些免疫参数时缺乏相互作用，表明它们对免疫系统的影响可能除雌激素受体外还涉及其他机制。
