Marks S C, Mattox D E, Casero R A
Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins Hospital, Baltimore, Maryland 21205.
Hear Res. 1991 Jun;53(2):230-6. doi: 10.1016/0378-5955(91)90057-g.
Difluoromethylornithine (DFMO) is a novel antineoplastic agent that was associated with an unexpected hearing loss in Phase II clinical trials. DFMO interferes with polyamine synthesis by inhibition of the enzyme ornithine decarboxylase (ODC). The objective of the current study was to establish a methodology to determine the effect of DFMO on polyamine levels and ODC activity in the cochlea. Guinea pigs received DFMO in their drinking water and were tested for auditory brainstem response threshold shifts. The organ of Corti, the lateral wall, and the acoustic nerve were assayed for both ODC activity and polyamine levels. In DFMO treated animals there was an inhibition of ODC activity in cochlear tissues as well as in intestinal mucosa. In addition, a significant depletion of cochlear polyamines was observed in the treatment animals. This study suggests that systemically administered DFMO inhibits ODC activity and interferes with polyamine synthesis in the cochlea.
二氟甲基鸟氨酸（DFMO）是一种新型抗肿瘤药物，在II期临床试验中出现了意外的听力损失。DFMO通过抑制鸟氨酸脱羧酶（ODC）来干扰多胺合成。本研究的目的是建立一种方法，以确定DFMO对耳蜗中多胺水平和ODC活性的影响。豚鼠饮用含DFMO的水，并检测听觉脑干反应阈值变化。对柯蒂氏器、外侧壁和听神经进行ODC活性和多胺水平检测。在接受DFMO治疗的动物中，耳蜗组织以及肠黏膜中的ODC活性均受到抑制。此外，在治疗组动物中观察到耳蜗多胺显著减少。本研究表明，全身给药的DFMO可抑制耳蜗中的ODC活性并干扰多胺合成。
