White K L, Germolec D R, Musgrove D L, Delclos K B, Newbold R R, Weis C, Guo T L
Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA, USA.
J Immunotoxicol. 2004 Apr;1(2):113-21. doi: 10.1080/15476910490518893.
The potential effects of the fungicide vinclozolin (VCZ) on the immune system were evaluated in F(0) (dams) and F(1) generations of Sprague Dawley rats exposed to a soy-free diet containing VCZ at 10, 150 and 750 ppm. In dams, exposure to VCZ at the highest concentration from gestation day 7 to postpartum day 51 (65 days total exposure) produced a significant increase in the numbers of splenocytes, B cells, T cells, helper T cells and cytotoxic T cells and a decrease in the percentage of NK cells. In F(1) males, exposure to VCZ gestationally, lactationally and through feed from postnatal day 22 to 64 (78 days total exposure) produced no effect on spleen or thymus weights or splenocyte subsets. However, increases in the spleen IgM antibody-forming cell response to sheep red blood cells (150 and 750 ppm) and the activity of NK cells (150 ppm) were observed. In F(1) females, exposure to VCZ produced a decrease in the activity of NK cells in all the treatment groups. Although decreases in the number of cytotoxic T cells (150 ppm) and the percentages of NK cells (10 ppm) and cytotoxic T cells (150 ppm) were also observed, the lack of a dose-related response suggested that these findings might not be biologically meaningful. In conclusion, these results demonstrate that exposure to VCZ at the concentrations tested modulates the immune responses in Sprague Dawley rats. Furthermore, the differential effect of VCZ in F(1) male and female rats is consistent with the reported anti-androgenic properties of VCZ.
在食用含10 ppm、150 ppm和750 ppm乙烯菌核利（VCZ）的无大豆饮食的F(0)代（母鼠）和F(1)代斯普拉格-道利大鼠中，评估了杀菌剂乙烯菌核利（VCZ）对免疫系统的潜在影响。在母鼠中，从妊娠第7天到产后第51天暴露于最高浓度的VCZ（总共暴露65天），导致脾细胞、B细胞、T细胞、辅助性T细胞和细胞毒性T细胞数量显著增加，自然杀伤细胞百分比降低。在F(1)代雄性大鼠中，在妊娠期、哺乳期以及从出生后第22天到64天通过饲料暴露于VCZ（总共暴露78天），对脾脏或胸腺重量或脾细胞亚群没有影响。然而，观察到脾脏对绵羊红细胞的IgM抗体形成细胞反应增加（150 ppm和750 ppm）以及自然杀伤细胞活性增加（150 ppm）。在F(1)代雌性大鼠中，暴露于VCZ导致所有治疗组的自然杀伤细胞活性降低。尽管还观察到细胞毒性T细胞数量减少（150 ppm）以及自然杀伤细胞百分比（10 ppm）和细胞毒性T细胞百分比（150 ppm）降低，但缺乏剂量相关反应表明这些发现可能没有生物学意义。总之，这些结果表明，在所测试的浓度下暴露于VCZ会调节斯普拉格-道利大鼠的免疫反应。此外，VCZ对F(1)代雄性和雌性大鼠的不同影响与报道的VCZ抗雄激素特性一致。
