Academic Journal
Relationships between DNA Incorporation, Mutant Frequency, and Loss of Heterozygosity at the TK Locus in Human Lymphoblastoid Cells Exposed to 39-Azido-39-deoxythymidine
| العنوان: | Relationships between DNA Incorporation, Mutant Frequency, and Loss of Heterozygosity at the TK Locus in Human Lymphoblastoid Cells Exposed to 39-Azido-39-deoxythymidine |
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| المؤلفون: | Quanxin Meng, Ting Su, Ofelia A. Olivero, Miriam C. Poirier, Xiaochu Shi |
| المساهمون: | The Pennsylvania State University CiteSeerX Archives |
| المصدر: | http://toxsci.oxfordjournals.org/content/54/2/322.full.pdf. |
| سنة النشر: | 1999 |
| المجموعة: | CiteSeerX |
| مصطلحات موضوعية: | Key Words, 3*-azido-3*-deoxythymidine, human lymphoblastoid |
| الوصف: | 3*-Azido-3*-deoxythymidine (AZT), a thymidine analogue widely used in the treatment of AIDS patients and for prevention of the onset of AIDS in HIV-seropositive individuals, causes tumors in mice exposed as adults or in utero. The purpose of this study was to investigate the potential mechanisms of AZT mutagenicity and car-cinogenicity by quantifying the incorporation of AZT into cellular DNA, measuring AZT-induced thymidine kinase (TK) mutant fre-quencies (Mfs), and determining the percentage of loss of heterozy-gosity (LOH) in spontaneous or AZT-induced TK mutants in the human lymphoblastoid cell line, TK6. Cells were exposed to 300 mM AZT for 0, 1, 3, or 6 days, or to 0, 33, 100, 300, or 900 mM AZT for 3 days (n 5 5 flasks/group). The effects of exposure concentration on incorporation of AZT into cellular DNA were evaluated by an AZT radioimmunoassay, and the effects of duration and concentration of AZT exposure on the TK Mfs were assessed by a cell-cloning assay. AZT was incorporated into DNA in a dose-related manner at con-centrations up to 300 mM, above which no further increase was observed. TK Mf increased with the extended duration and with incremental concentrations of AZT exposure. There was a positive correlation (P 5 0.036, coefficient 5 0.903) between AZT-DNA incorporation and AZT-induced TK Mfs, suggesting that AZT incor-poration into cellular DNA has a direct role in the genotoxicity of AZT. Southern blot analyses indicated that 84 % (6.2 3 10–6/7.4 3 10–6) of AZT-induced mutants were attributable to LOH, consistent with the known mechanism of AZT as a DNA chain terminator. Considering the importance of LOH in human carcinogenesis, AZT-induced LOH warrants further study. |
| نوع الوثيقة: | text |
| وصف الملف: | application/pdf |
| اللغة: | English |
| Relation: | http://citeseerx.ist.psu.edu/viewdoc/summary?doi=10.1.1.571.3245; http://toxsci.oxfordjournals.org/content/54/2/322.full.pdf |
| الاتاحة: | http://citeseerx.ist.psu.edu/viewdoc/summary?doi=10.1.1.571.3245 http://toxsci.oxfordjournals.org/content/54/2/322.full.pdf |
| Rights: | Metadata may be used without restrictions as long as the oai identifier remains attached to it. |
| رقم الانضمام: | edsbas.EC6841A2 |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |