STRAIN DIFFERENCES IN RESPONSE OF SPRAGUE-DAWLEY AND LONG EVANS HOODED RATS TO THE TERATOGEN NITROFEN
STRAIN DIFFERENCES IN RESPONSE OF SPRAGUE-DAWLEY AND LONG EVANS HOODED RATS TO THE TERATOGEN NITROFEN
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DOI：
10.1002/tera.1420340211
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发表时间：
1986-10-01
期刊：
影响因子：
--
通讯作者：
MANSON, JM
中科院分区：
文献类型：
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作者：
KANG, YJ;ZOLNA, L;MANSON, JM
在啮齿动物器官形成过程中给予除草醚（2，4-二氯-4 ''-硝基二苯醚）可导致新生儿死亡，并伴有肺发育不全、疝气、心脏畸形和肾积水。据报告，不同品系的大鼠Long Evans Hooded（莱赫）和Sprague-Dawley（SD）对产前暴露具有不同的畸形反应，这可能是由于真实品系差异、不同的暴露水平和暴露时间或使用不同的内脏畸形检测方法所致。在本研究中，莱赫、SD和“病毒抗体阴性”SD（VAN-SD）大鼠在妊娠第6-15天通过管饲法相同地暴露于0、6.25、12.5或25 mg/kg/天的玉米油中的氮。在足月时，通过Wilson刀片切片法检查一半窝仔，通过改良的斯台普斯法检查其余窝仔的新鲜内脏。这两种方法同样敏感的检测膈肌，肾脏和肺部异常，而心脏畸形更频繁地发现新鲜的内脏检查。在任何剂量下，各品系的总畸形频率均无差异，但各品系的畸形模式存在显著差异。SD和VAN-SD大鼠对所有畸形的反应相似，但膈肌和肺畸形的发生率显著高于莱赫大鼠。相反，与SD和VAN-SD大鼠相比，莱赫大鼠的肾脏异常水平显著升高，而心脏畸形的频率较低，且各品系之间相当。这些结果表明，真正的应变差异存在于产前暴露于除草醚，可能是基于胚胎易感性的遗传差异产生的畸形模式。
Administration of nitrofen (2,4-dichloro-4''-nitrodiphenyl ether) during organogenesis in rodents produces neonatal lethality accompanied by lung hypoplasia, diaphragmatic hernias, heart anomalies, and hydronephrosis. Different strains of rats, Long Evans Hooded (LEH) and Sprague-Dawley (SD), are reported to have different malformation responses to prenatal exposure, which could be due to true strain differences, to different levels and times of exposure, or to the use of different methods for detecting visceral malformations. In the present study, LEH, SD, and "virus-antibody-negative" SD (VAN-SD) rats were identically exposed to 0, 6.25, 12.5, or 25 mg/kg/day of nitrogen by gavage in corn oil on days 6-15 of gestation. At term, half of the litter was examined by the Wilson method of razorblade sectioning and the remainder by a modified Staples method of fresh visceral examination. The two methods were equally sensitive for detecting diaphragm, kidney, and lung anomalies, whereas heart malformations were more frequently identified with fresh visceral examination. The frequency of total malformations did not vary across strains at any dose, but there were substantial differences in the pattern of malformations in each strain. SD and VAN-SD rats responded similarly for all malformations, but had significantly higher incidences of diaphragm and lung anomalies than LEH rats. Conversely, LEH rats had significantly elevated levels of kidney anomalies compared to SD and VAN-SD rats, whereas frequency of heart malformations was low and comparable across strains. These results suggest that true strain differences exist in the pattern of malformation produced by prenatal exposure to nitrofen that may be based on genetic differences in embryonic susceptibility.