Rebert C S, Pryor G T, Frick M S
J Appl Toxicol. 1984 Dec;4(6):330-8. doi: 10.1002/jat.2550040610.
The effects of the antineoplastic drugs vincristine, maytansine and cis-platinum were studied to determine the appropriateness of a behavioral and electrophysiological test battery for characterizing the neurotoxicity of such therapeutic compounds. Single- and repeated-dose studies in rats were performed initially, to establish doses for the subchronic neurobehavioral study. Measurements obtained in the subchronic study included body weight, rectal temperature, forelimb and hindlimb grip strengths; performance of a multisensory conditional avoidance response task and other behavioral tests; and a series of evoked responses (ventral caudal nerve action potential, brainstem auditory response and responses from other modalities). The drugs were injected intraperitoneally 5 days per week for 7 weeks. The rats were tested weekly during baseline, treatment and recovery phases. Each drug caused a different pattern of effects, but they all altered body weight, rectal temperature, peripheral nerve conduction velocity, the somatosensory evoked potential and undifferentiated motor activity. cis-Platinum was the most toxic, and maytansine was the least toxic. The results indicated that some elements of the test battery were useful for evaluating the neurotoxicity of anticancer drugs. However, other tests - notably, a test of negative geotaxis and the cortical auditory evoked response - were unreliable.
研究了抗肿瘤药物长春新碱、美登素和顺铂的作用，以确定一套行为和电生理测试组合用于表征此类治疗性化合物神经毒性的适用性。最初在大鼠中进行了单剂量和重复剂量研究，以确定亚慢性神经行为研究的剂量。在亚慢性研究中获得的测量指标包括体重、直肠温度、前肢和后肢握力；多感官条件回避反应任务及其他行为测试的表现；以及一系列诱发反应（尾腹侧神经动作电位、脑干听觉反应和其他模式的反应）。每周5天腹腔注射药物，持续7周。在基线期、治疗期和恢复期每周对大鼠进行测试。每种药物产生了不同的效应模式，但它们都改变了体重、直肠温度、外周神经传导速度、体感诱发电位和未分化的运动活动。顺铂毒性最大，美登素毒性最小。结果表明，测试组合中的一些元素可用于评估抗癌药物的神经毒性。然而，其他测试——尤其是负趋地性测试和皮层听觉诱发反应测试——不可靠。
