Chlorpyrifos interferes with cell development in rat brain regions
Chlorpyrifos interferes with cell development in rat brain regions
复制标题
DOI：
10.1016/s0361-9230(96)00436-4
复制
发表时间：
1997-01-01
影响因子：
3.8
通讯作者：
Slotkin, TA
中科院分区：
文献类型：
--
作者：
Campbell, CG;Seidler, FJ;Slotkin, TA
毒死蜱是最广泛使用的杀虫剂之一，在发育过程中表现出比成年期更大的毒性。我们给新生大鼠施用了超过全身毒性阈值的毒死蜱，并使用细胞堆积密度和细胞数量（DNA浓度和含量）以及细胞大小（蛋白质/DNA比率）标记检查了发育中的大脑区域（脑干、前脑、小脑）对细胞发育的干扰迹象。出生后1 ~ 4天给予5 mg/kg毒死蜱的新生大鼠死亡率显著，存活鼠脑干细胞严重丢失；尽管脑干和前脑都具有相似的胆碱能投射，但在1 mg/kg剂量下没有观察到这种影响，该剂量不会损害生存或生长，也没有任何对前脑的不良影响。当毒死蜱在11-14天施用时，细胞损失的主要目标从脑干转移到前脑，在这种情况下，剂量的影响并不影响生存或生长，前脑细胞数量的损失发生在15至20天龄之间，而不是在毒死蜱治疗期间。小脑与其他区域的不同之处在于，在毒死蜱暴露后的早期或后期，小脑显示出DNA的短期升高；然而，随着其他区域细胞的减少，这些值随之回归到亚正常水平。因此，毒死蜱可能导致细胞延迟死亡。虽然富含胆碱能投射的区域，如脑干和前脑，可能比非胆碱能区域（小脑）受到更大的影响，但每个区域的成熟时间表（脑干最早，前脑居中，小脑最后）在设定易损性窗口方面似乎更重要。这些结果表明，即使在生长或生存不受影响的情况下，毒死蜱也会在发育中的大脑中产生细胞缺陷，从而导致行为异常。(C) 1997爱思唯尔科学有限公司
Chlorpyrifos, one of the most widely used pesticides, exhibits greater toxicity during development than in adulthood. We administered chlorpyrifos to neonatal rats in doses spanning the threshold for systemic toxicity and examined developing brain regions (brainstem, forebrain, cerebellum) for signs of interference with cell development using markers for cell packing density and cell number (DNA concentration and content) and cell size (protein/DNA ratio). Neonatal rats given 5 mg/kg of chlorpyrifos on postnatal days 1-4 showed significant mortality and the survivors exhibited severe cell loss in the brainstem; brainstem growth was maintained by enlargement of the remaining cells, This effect was not seen at 1 mg/kg, a dose that did not compromise survival or growth, nor was there any adverse effect at either dose in the forebrain, despite the fact that both brainstem and forebrain possess comparable cholinergic projections. When chlorpyrifos was administered later, on days 11-14, the major target for cell loss shifted from the brainstem to the forebrain and in this case, effects were seen at doses that did not compromise survival or growth, The loss of forebrain cell number occurred between 15 and 20 days of age rather than during the chlorpyrifos treatment. The cerebellum differed from the other regions in that it showed short-term elevations of DNA after chlorpyrifos exposure in either early or late postnatal periods; nevertheless, values then regressed to subnormal in parallel with the loss of cells in other regions. Thus, chlorpyrifos likely causes delayed cell death. Although regions rich in cholinergic projections, such as brainstem and forebrain, may be more affected than noncholinergic regions (cerebellum), the maturational timetable of each region (brainstem earliest, forebrain intermediate, cerebellum last) appears to be more important in setting the window of vulnerability. These results indicate that, even when growth or survival are unaffected, chlorpyrifos produces cellular deficits in the developing brain that could contribute to behavioral abnormalities. (C) 1997 Elsevier Science Inc.