Abstract:
:Azidothymidine (AZT) is a nucleoside reverse transcriptase inhibitor (NRTI) that is used for reducing mother-to-child transmission of human immunodeficiency virus I. Combinations of AZT and 3'-thiacytidine (3TC) are even more effective than AZT alone. AZT, however, is a mutagen and carcinogen in rodent models and 3TC can increase the genotoxicity of AZT. Since p53 plays a key role in human and mouse tumorigenesis, p53-haplodeficient mice are currently being evaluated as a model for assessing the carcinogenicity of perinatal exposure to NRTIs. In the present study, male C57BL/6 p53(+/+) and p53(-/-) mice were mated with C3H p53(+/+) females; the pregnant females were treated on gestation day 12 through parturition with 40, 80, and 160 mg/kg of AZT or a combination of 160 mg/kg AZT and 100 mg/kg 3TC (AZT-3TC); the p53(+/+) and p53(+/-) offspring were treated daily after birth through postnatal day (PND) 28. The frequencies of micronucleated reticulocytes (MN-RETs) and micronucleated normochromatic erythrocytes (MN-NCEs) were determined on PND1, PND10, and PND28; the frequency of Hprt mutant lymphocytes was measured on PND28. The frequencies of MN-RETs and MN-NCEs were increased in treated animals at all time points; there were no differences in the responses of p53(+/+) and p53(+/-) animals treated with identical doses of NRTIs. After correction for clonal expansion, both AZT and AZT-3TC treatments induced small but significant increases in the frequency of Hprt mutant lymphocytes in p53(+/-) mice, but not in p53(+/+) mice. The data indicate that p53 haplodeficiency affects the genotoxicity of NRTIs; thus, p53(+/-) mice may be a sensitive model for evaluating the carcinogenicity of perinatal exposure to NRTIs.
journal_name
Environ Mol Mutagenjournal_title
Environmental and molecular mutagenesisauthors
Dobrovolsky VN,Shaddock JG,Mittelstaedt RA,Bishop ME,Lewis SM,Lee FW,Aidoo A,Leakey JE,Dunnick JK,Heflich RHdoi
10.1002/em.20280subject
Has Abstractpub_date
2007-04-01 00:00:00pages
270-82issue
3-4eissn
0893-6692issn
1098-2280journal_volume
48pub_type
杂志文章abstract::Data on human trisomic conceptuses suggest that the extra chromosome commonly has a maternal origin, and the amount and position of crossing-over on nondisjoined chromosomes is commonly altered. These observations may provide important clues to the etiology of human germ cell aneuploidy, especially in regard to evalua...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章,评审
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journal_title:Environmental and molecular mutagenesis
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journal_title:Environmental and molecular mutagenesis
pub_type: 临床试验,杂志文章
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journal_title:Environmental and molecular mutagenesis
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journal_title:Environmental and molecular mutagenesis
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journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
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journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
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更新日期:2008-12-01 00:00:00
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journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
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journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
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journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.22032
更新日期:2016-08-01 00:00:00
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journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
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更新日期:2013-12-01 00:00:00
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journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
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更新日期:2001-01-01 00:00:00
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journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
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更新日期:1998-01-01 00:00:00
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journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.22422
更新日期:2021-01-11 00:00:00
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journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:
更新日期:1999-01-01 00:00:00
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journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.2850180105
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journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.2850180204
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journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/(SICI)1098-2280(1996)27:1<67::AID-EM9>3.0.
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pub_type: 杂志文章
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journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/(SICI)1098-2280(1996)28:4<325::AID-EM5>3.0
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更新日期:2006-01-01 00:00:00
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journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
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journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
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更新日期:2008-12-01 00:00:00
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journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
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journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
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journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.10210
更新日期:2004-01-01 00:00:00
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journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
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更新日期:2009-01-01 00:00:00
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journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.2850160302
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