A comparison of behavioral and anatomical measures of hydroxyurea induced abnormalities.

A comparison of behavioral and anatomical measures of hydroxyurea induced abnormalities.
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羟基脲引起的异常的行为和解剖学测量的比较。

DOI:
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发表时间:
1978
期刊:
Teratology
影响因子:
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通讯作者:
R. Butcher
R. Butcher
中科院分区:
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文献类型:
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作者:
R. L. Brunner;M. McLean;C. Vorhees;R. Butcher

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在妊娠第6、9、12、15和18天,对妊娠母鼠给予一次(150 mg/kg)具有抗有丝分裂作用的药物--羟基脲。从2日龄开始对这些母鼠加对照受试者的窝仔进行行为测试,直至21日龄处死。进行了以下测试:(i)水面扶正,(ii)空中扶正,(iii)悬崖回避,(iv)游泳发展,(v)旋转和(vi)惊吓。在扶正,悬崖和惊吓一窝进行了测试,直到所有成员显示标准的反应,年龄提供了统计分析的分数。在游泳和旋转,时间和频率的措施进行了分析。对任何行为指标均无显著给药效应。在妊娠第9天注射的母鼠幼鼠出现脑积水和小眼症。后一种观察结果通过该组在21日龄时显著降低的眼重得到证实。区域脑重量测量没有区分各组。脑积水与脑组织坏死、体重减轻、行为迟缓和早期死亡密切相关。结果表明,更大的灵敏度的断言相比,形态学的措施,在筛选药物危害需要进行资格。提出了一个逐步筛选程序,并建议行为研究需要包括脑病理学评估作为功能和结构方法之间的桥梁。
Hydroxyurea, a drug which has antimitotic effects was administered once (150 mg/kg) to pregnant dams on the sixth, ninth, twelfth, fifteenth and eighteenth day of gestation. Litters of these dams plus control subjects were tested behaviorally from two days of age until sacrificed at 21 days of age. The following tests were conducted: (i) surface righting, (ii) mid-air righting, (iii) cliff avoidance, (iv) swimming development, (v) pivoting and (vi) startle. In righting, cliff and startle a litter was tested until all members displayed a criterion response and that age provided the score for statistical analysis. In swimming and pivoting, time and frequency measures were analyzed. There were no significant treatment effects on any of the behavioral measures. Rat pups of dams injected on Day 9 of pregnancy evidenced hydrocephaly and micropthalmia. The latter observation was confirmed by eye weights which were significantly reduced in this group at 21 days of age. Regional brain weight measurements did not distinguish among the groups. Hydrocephaly was variably associated with necrotic brain tissue, loss in weight, behavioral delays and early death. The results suggested that the assertion of greater sensitivity of behavioral compared to morphological measures in screening for drug hazards needs to be qualified. A step wise procedure for screening was proposed and it was suggested that behavioral studies need to include assessments of brain pathology as a bridge between functional and structural approaches.