| Autor: |
OSHIRO, Y., PIPER, C. E., SOELTER, S. G., BALWIERZ, P. S., GARRIOTT, M. L. |
| Zdroj: |
Fundamental & Applied Toxicology; Aug1992, Vol. 18 Issue 4, p491-498, 8p |
| Abstrakt: |
()-5-(2-bromovinyl)-2′-deoxyuridine (BVDU) is a 5-substituted 2′-deoxyuridine antiviral compound that inhibits thymidylate synthetase. The selectivity of BVDU for virus-infected cells has been attributed to phosphorylation of BVDU by a virus-induced thymidine kinase. Since the closely related compounds 5-bromo-2′-deoxyuridine and 5-iodo-2′-deoxyuridine are and mutagens, BVDU was tested for genotoxic activity in bacterial and mammalian cell mutation assays as well as in assays measuring DNA damage/repair and clastogenic activity. Mutation assays with BVDU at concentrations ranging from 10 to 5000 μg/plate using strains TA1535, TA1537, TA1538, TA98, and TA100 were negative, both with and without S9 activation. BVDU was also negative in the rat hepatocyte unscheduled DNA synthesis assay at concentrations of 750 and 1000 μg/ml. In contrast, BVDU was positive in the L5178Y TK mouse lymphoma mutation assay without S9 activation at five concentrations ranging from 500 to 2000 μg/ml. A Chinese hamster ovary cell (CHO)/hypoxanthine guanine phosphoribosyl transferase gene mutation assay conducted without S9 over similar concentrations was negative. However, micronucleus induction by BVDU was detected with out S9 activation at concentrations between 500 and 1750 μg/ml using both CHO and L5178Y cells. These results indicate that BVDU is a potential human clastogen. [ABSTRACT FROM PUBLISHER] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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