Mutagenicity and loss of heterozygosity at the APRT locus in human lymphoblastoid cells exposed to 3'-azido-3'-deoxythymidine
| Autor: | Xiaochu Shi, Vernon E. Walker, Quanxin Meng, Andrew J. Grosovsky |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Antimetabolites
Cell Survival viruses Health Toxicology and Mutagenesis Adenine Phosphoribosyltransferase Adenine phosphoribosyltransferase Loss of Heterozygosity Toxicology Cell Line Loss of heterozygosity Zidovudine immune system diseases Genetics medicine Humans heterocyclic compounds Genetics (clinical) B-Lymphocytes Dose-Response Relationship Drug biology Mutagenicity Tests Lymphoblast virus diseases DNA biochemical phenomena metabolism and nutrition Virology Molecular biology Mutagenesis Thymidine kinase Cell culture Hypoxanthine-guanine phosphoribosyltransferase Mutation biology.protein Phosphoribosyltransferase Polymorphism Restriction Fragment Length medicine.drug |
| Zdroj: | Mutagenesis. 15:405-410 |
| ISSN: | 1464-3804 |
| DOI: | 10.1093/mutage/15.5.405 |
| Popis: | Previous experiments in our research group showed that 3'-azido-3'-deoxythymidine (AZT) caused increased mutant frequencies (Mfs) at the X-linked hypoxanthine-guanine phosphoribosyltransferase (HPRT) and the autosomal thymidine kinase (TK) genes in human lymphoblastoid cells and that there was a significant positive correlation between AZT incorporation into cellular DNA and AZT-induced TK Mfs. In the current study, the mutagenicity of AZT was further evaluated at the autosomal adenine phosphoribosyltransferase (APRT) gene. AZH1 cells, a human lymphoblastoid cell line heterozygous at the APRT locus, were exposed to 300 microM AZT for 0, 1, 3 or 6 days or to 0, 33, 100, 300 or 900 microM AZT for 3 days (n = 5 flasks/group). A cell cloning assay was used to quantitate APRT Mfs. AZT-induced APRT Mf increased with extended duration and with incremental concentrations of AZT exposure. There was a positive correlation (P = 0.022, coefficient = 0.93) between AZT incorporation into DNA and AZT-induced APRT Mfs. RFLP analyses indicated that AZT exclusively induced loss of heterozygosity in APRT mutants. These results, which are consistent with findings on the mutagenicity of AZT at the HPRT and TK genes, indicate the need for further investigations on the potential long-term side effects of AZT on humans, especially those who receive AZT for a prophylactic reason. |
| Databáze: | OpenAIRE |
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