Abstract：
BACKGROUND:Zidovudine (3'-azido-3'-deoxythymidine, AZT), administered to pregnant women alone or in combination with other antiretroviral drugs, greatly reduces the mother-to-child transmission of HIV-1. The potential genotoxicity of these molecules is underestimated and wide-ranging evaluation of its biological and clinical consequences is required. METHODS:We investigated the nuclear organization of constitutive heterochromatin, a major domain participating in epigenetic regulation, in uninfected infants born to HIV-1-infected mothers treated with zidovudine and/or other nucleoside reverse transcriptase inhibitors (NRTIs) during pregnancy. We studied the organization of chromosome 1 heterochromatin (1q12) in peripheral leukocytes of 25 HIV-1-uninfected children (newborn to 9 years old): children born to HIV-1-infected mothers exposed to zidovudine and/or other NRTIs (n=15), children born to HIV-1-infected mothers not exposed to any NRTIs (n=6) and children born to HIV-1-uninfected mothers (n=4). RESULTS:Results differed significantly between NRTI-exposed and -unexposed children. By contrast, there was no difference between NRTI-unexposed children born to HIV-1-infected mothers and children born to HIV-uninfected mothers. The anomaly persisted in lymphocytes cultured for 48 h. There was no evidence of abnormal DNA methylation, a major feature of constitutive heterochromatin and associated with the loss of its structure. In a complementary sample of children, analysis of chromosome 11 and 16 heterochromatin suggests that the defect affects most of the other heterochromatic sites of the human genome. The heterochromatin defect persists long after the end of the exposure and appears in leukocytes of both myeloid and lymphoid lineages, suggesting that haematopoietic stem cells are affected.
journal_name
Antivir Therjournal_title
Antiviral therapyauthors
Senda S,Blanche S,Costagliola D,Cibert C,Nigon F,Firtion G,Floch C,Parat S,Viegas-Péquignot Esubject
Has Abstractpub_date
2007-01-01 00:00:00pages
179-87issue
2eissn
1359-6535issn
2040-2058journal_volume
12pub_type
杂志文章abstract：:The study was carried out to evaluate the therapeutic effects of zanamivir, a highly selective, potent and specific inhibitor of influenza A and B virus neuraminidases, in adult patients with acute influenza-like illness. Patients who presented within 36 h of the onset of influenza-like symptoms were randomly assigned...
journal_title：Antiviral therapy
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doi：
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journal_title：Antiviral therapy
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更新日期：2008-01-01 00:00:00
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pub_type： 杂志文章
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更新日期：2011-01-01 00:00:00
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更新日期：2001-03-01 00:00:00
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pub_type： 杂志文章,多中心研究,随机对照试验
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更新日期：2011-01-01 00:00:00
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更新日期：2014-01-01 00:00:00
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pub_type： 杂志文章,多中心研究
doi：10.3851/IMP3219
更新日期：2018-01-01 00:00:00
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journal_title：Antiviral therapy
pub_type： 临床试验,杂志文章,多中心研究
doi：
更新日期：2006-01-01 00:00:00
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pub_type： 杂志文章
doi：
更新日期：2003-04-01 00:00:00
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pub_type： 杂志文章,meta分析,评审
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更新日期：2014-01-01 00:00:00
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journal_title：Antiviral therapy
pub_type： 杂志文章
doi：
更新日期：2009-01-01 00:00:00
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pub_type： 杂志文章,随机对照试验
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更新日期：2010-01-01 00:00:00
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pub_type： 杂志文章
doi：
更新日期：2009-01-01 00:00:00
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pub_type： 杂志文章,多中心研究
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更新日期：2018-01-01 00:00:00
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pub_type： 临床试验,杂志文章
doi：
更新日期：2005-01-01 00:00:00
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journal_title：Antiviral therapy
pub_type： 杂志文章,评审
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更新日期：2007-01-01 00:00:00
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pub_type： 杂志文章,收录出版
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更新日期：2013-01-01 00:00:00
