Gender-based profiles of developmental immunotoxicity to lead in the rat: Assessment in juveniles and adults
Gender-based profiles of developmental immunotoxicity to lead in the rat: Assessment in juveniles and adults
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DOI：
10.1080/15287390152543708
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发表时间：
2001-10-12
期刊：
影响因子：
--
通讯作者：
Dietert, RR
中科院分区：
文献类型：
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作者：
Bunn, TL;Parsons, PJ;Dietert, RR
在胚胎发育过程中低水平暴露后，在幼鸡和成年大鼠中观察到了由重金属铅 (Pb) 引起的免疫毒性的性别差异，为了更好地定义与剂量相关的基于性别的差异，在子宫内暴露于 Pb 时，在 F 344 大鼠随意暴露于低浓度 Pb（0、50、700 或 250 ppm Pb）后，检查了潜在的差异敏感性。妊娠。对青少年（5 周龄）和年轻人（13 周龄）进行免疫评估。在检测的最高铅浓度（250 ppm）下，两个年龄段的女性迟发型超敏反应（DTH）均低于性别匹配的对照组；在13周龄而非5周龄时，相对脾脏重量和相对中性粒细胞数量增加，而相对和绝对单核细胞数量以及相对嗜碱性粒细胞数量减少。相比之下，接受 250 ppm Pb 处理的雄性在这些终点上没有差异。在子宫内暴露于 100 ppm Pb 时，13 周龄雌性的单核细胞相对和绝对数量再次下降，而相对中性粒细胞数量增加，但 DTH 反应没有变化。雄性（含 100 ppm Pb）在 5 周龄而非 13 周龄时，相对中性粒细胞数量增加，相对淋巴细胞数量减少，亚硝酸盐产量短暂增加。妊娠期暴露于 50 ppm Ph 后，在评估的任一发育年龄的男性或女性中观察到最小的免疫毒性作用。这些结果表明，妊娠期 Ph 暴露后存在不同性别的免疫毒性特征，具体取决于母鼠施用的 Pb 浓度。母鼠在子宫内暴露于 250 ppm 的铅会导致雌性比雄性更严重的免疫毒性，雄性对较低浓度的铅并不比雌性更敏感。由于 50 ppm 暴露产生的变化很小，因此这些数据可以提供信息来确定子宫内 Pb 暴露的未观察到不良影响水平 (NOAEL)。此外，白色的大多数影响在青少年和成人阶段都很明显，一些变化直到在成人身上测量才完全明显。大多数变化都是持久的，只有一个例外（雄性亚硝酸盐水平为 100 ppm）。
Gender-based differences in immunotoxicity induced by the heavy metal lead (Pb) have been observed both in the juvenile chicken and the adult rat following low-level exposure during embryonic development, To better define the gender-based differences, as related to dose following In utero exposure to Pb, potential differential sensitivities were examined after exposure of F 344 rats to low concentrations of Pb (0, 50, 700, or 250 ppm Pb) ad libitum throughout gestation. Immune assessment was performed in juveniles (5 wk old) and young adults (13 wk old). At the highest (250 ppm) Pb concentration examined, the delayed-type hypersensitivity (DTH) response was depressed in females relative to gender-matched controls at both ages; relative spleen weights and relative neutrophil numbers were increased while relative and absolute monocyte numbers and relative basophil numbers were decreased at 13 but not 5 wk of age. In contrast, 250 ppm Pb-treated males did not differ in these endpoints. With in utero exposure to 100 ppm Pb, 13-wk-old females again had decreased relative and absolute monocyte numbers and increased relative neutrophil numbers, although the DTH response was unchanged. Males (with 100 ppm Pb) had increased relative neutrophil numbers, decreased relative lymphocytes, and transiently increased nitrite production seen at 5, but not 13, wk of age. After gestational exposure to 50 ppm Ph, minimal immunotoxic effects were observed in either males or females at either developmental age assessed. These results suggest that differential gender-based immunotoxicity profiles exist after gestational Ph exposure depending on the concentration of Pb administered to the dam. In utero exposure of dams to 250 ppm Pb results in more profound immunotoxicity in females than males, Males are not more sensitive to lower concentrations of Pb than females. Since the 50 ppm exposure produced minimal changes, these data may provide information to establish a no-observed-adverse-effect level (NOAEL) for in utero exposure to Pb. Additionally, white most effects were evident at both juvenile and adult ages, some changes were not fully evident until measured in the adult. Most changes were persistent with only one exception (male nitrite levels at 100 ppm).