Thymidine kinase deficient cells with decreased TTP pools are hypersensitive to DNA alkylating agents
| Autor: | Stanton L. Gerson, Lili Liu, Kenshi Furusho, Yoshihiro Wakazono, Masaru Kubota |
|---|---|
| Rok vydání: | 1996 |
| Předmět: |
Hypoxanthine Phosphoribosyltransferase
Methylnitronitrosoguanidine Guanine Leukemia T-Cell Ethyl methanesulfonate Cell Survival Antineoplastic Agents HL-60 Cells Biology Toxicology Thymidine Kinase O(6)-Methylguanine-DNA Methyltransferase chemistry.chemical_compound Tumor Cells Cultured Genetics Humans Thymine Nucleotides Cytotoxic T cell Mutation frequency Cytotoxicity Antineoplastic Agents Alkylating Molecular Biology Methyltransferases Molecular biology chemistry Mutagenesis Thymidine kinase Cell culture Hypoxanthine-guanine phosphoribosyltransferase Ethyl Methanesulfonate Mutagens Alkyltransferase |
| Zdroj: | Mutation Research/DNA Repair. 362:119-125 |
| ISSN: | 0921-8777 |
| DOI: | 10.1016/0921-8777(95)00042-9 |
| Popis: | The effect of mutational loss of thymidine kinase (TK) on the sensitivity to alkylating agents was investigated in promyelocytic, HL-60, and T-lymphoblastoid, Molt-3, human leukemia cell lines. Although both cell lines exhibited approx. 1% residual TK activity, only HL-60 TK deficient cells had a decreased intracellular TTP pool, i.e., 20% of that of the wild-type. When treated with N -methyl- N′ -nitronitrosoguanidine or ethyl methanesulfonate, HL-60 TK deficient cells showed significantly increased killing and mutation frequencies at the hypoxanthine-guanine phosphoribosyl transferase (HGPRT) locus relative than did the wild-type. Pretreatment of cells with O 6 -benzylguanine, an inhibitor of O 6 -alkylguanine-DNA alkyltransferase, partially abolished those differences. Molt-3 wild-type and TK deficient cells had similar cell survivals and HGPRT mutation frequencies following treatment with alkylating agents. These results indicate that TK deficiency, only when a concomitant decrease of TTP pool is detected, plays a pivotal role in the sensitivity to the cytotoxic and mutagenic effects of alkylating agents. |
| Databáze: | OpenAIRE |
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