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【medical-news】化疗所致听力丧失的机理？
Researchers identify families of mice with mutations that cause problems similar to those found in children with hearing loss due to chemotherapy, as well as some adults with hearing loss
MEMPHIS, Tenn. – Sept. 26, 2006 -- Children with cancer who suffer hearing loss due to the toxic effects of chemotherapy might one day be able to get their hearing back through pharmacological and gene therapy, thanks to work done with mouse models at St. Jude Children's Research Hospital. Mice with a variety of genetic mutations that disrupt different parts of the ear will also help scientists understand age-related hearing loss in adults, as well as hearing loss caused by long-term exposure to loud noise, according to the researchers.
The investigators took the first step toward these ambitious goals by identifying 17 families of mice whose offspring carry one or more of a variety of mutations that cause them to lose the ability to hear high-frequency sounds, according to Jian Zuo, Ph.D., associate member of the St. Jude Department of Developmental Neurobiology. Zuo is senior author of a report on this work that appears in the October issue of Hearing Research.
These models will help scientists understand what happens in the ears of children who suffer ototoxicity (toxic damage to the inner ear due to chemotherapy) and eventually, which genes are responsible for that damage. "Our ongoing study of these mouse models will advance understanding of age-related and noise-induced hearing loss in humans--such as long-term exposure to loud music--which are similar to the damage that occurs in children receiving chemotherapy," Zuo said.
The mouse models of hearing loss were produced by the Tennessee Mouse Genome Consortium, a group of institutions across Tennessee that includes universities, several medical research centers and a national laboratory.
The consortium used ENU, a chemical that causes random mutations in sperm of mice that were subsequently mated with females. Offspring of this mating carried mutations in one or more specific spots in their DNA, Zuo explained. The random mutations caused a variety of disruptions of normal functions. However, only some of the mutations were likely to cause hearing loss, and it was not known which mutation each mouse had. Therefore, the St. Jude team screened more than 1,800 mice from 285 families using an auditory brainstem responses test. This test determines whether a particular mouse can respond to high frequencies by recording electrical activity from the hearing nerve and other parts of the brain in response to brief, high-frequency sounds. The team identified 17 families that showed evidence of hearing loss. The investigators then determined the types of ear abnormalities the mice had. The goal was to find the genes involved in different aspects of hearing loss.
"Now that we've identified the various problems in the ear that can contribute to hearing loss in these models, we can work back and look for specific mutations in these animals," Zuo said. "That will let us link specific mutations to specific disruptions in the ear that cause hearing loss. The long-term goal is to try to manipulate or replace those genes in order to overcome those problems."
Individual mutations might disrupt the work of a cascade of genes that cooperate to construct certain nerves or sections of the inner ear that sense sound; that stimulation is then turned into electrical impulses that go to the hearing center of the brain. Understanding how a specific mutation disrupts that cascade might lead to ways to repair the damage, Zuo said.
For example, one type of damage that occurs in children whose hearing is damaged by chemotherapy is loss of hair cells in the inner part of the ear. These cells sprout extremely fine hairs that move in response to sound waves and set up the electrical impulse that goes into the brain. These are the same cells damaged in adults by prolonged exposure to loud noise. "In the future we'd like to be able to prevent the loss of these hair cells or trigger their re-growth with some form of pharmacological or gene therapy intervention," Zuo said.
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St. Jude finds clues to hearing loss from chemotherapy
圣．吉德医院发现化疗导致听力丧失的线索 个人浅见：
1.MEMPHIS, Tenn. – Sept. 26, 2006 Tenn. 斑竹,由于第一次参加编译活动，并不知道具体怎样操作，我在9月25日已经将译文PM你了,并不知道要在这里发布,表示歉意,下次会注意,全文如下：
圣犹太研究院发现化疗能够导致听力丧失。
研究者们在变异的小白鼠家族找到的病因与由于化疗引起听力丧失的孩子和成人类似。
2006年9月26日，在美国田纳西州孟菲斯市，由于化疗的副作用引起听力丧失的患有肿瘤孩子们可能在一天内通过药理和基因治疗恢复他们的听力。这要感谢在圣犹太儿童研究院的老鼠模型研究，多种基因变异导致不同部位耳部损害的老鼠将帮助科学家们了解成人听力损害与年龄的关系以及长期低频率噪音导致听力损害的原因。
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作者:admin@医学,生命科学 2010-12-25 05:11
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