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Sister chromatid exchange induced by anti-herpes drugs
Abstract:
The rate of sister chromatid exchange induced by several anti-herpes agents was measured to assess their potential mutagenicity. The agents--5-iodo-deoxyuridine (IDU), 5-trifluoromethyl-deoxyuridine (TFT), and [E]-5-(2-bromovinyl)-deoxyuridine (BVDU)--were incubated at various concentrations with human lymphocytes and fibroblasts, and that rate of sister chromatid exchanges was measured. In lymphocytes and fibroblasts BVDU and IDU did not induce exchange except at concentrations of 50 mg/l, while TFT increased the rate of exchange at a concentration of 0.5 mg/l. The rate of sister chromatid exchange is a sensitive index of chromosomal damage, and these findings provide information on the safety of some of the antiherpes agents tested. TFT increased the rate of exchange at a concentration that coincides with its minimal antiviral concentration, but BVDU did not induce exchange at therapeutic concentrations.
Insights
This study assessed the mutagenicity of anti-herpes agents 5-iodo-deoxyuridine (IDU), 5-trifluoromethyl-deoxyuridine (TFT), and [E]-5-(2-bromovinyl)-deoxyuridine (BVDU). TFT showed mutagenic potential at low concentrations, while IDU and BVDU were only mutagenic at high levels.
Area of Science:
- Virology
- Genetics
- Toxicology
Background:
- Sister chromatid exchange (SCE) is a sensitive indicator of chromosomal damage and potential mutagenicity.
- Anti-herpes agents are crucial for treating viral infections, but their genotoxic potential requires careful evaluation.
- Understanding the mutagenicity of antiviral drugs is essential for ensuring patient safety.
Purpose of the Study:
- To evaluate the mutagenic potential of three anti-herpes agents: 5-iodo-deoxyuridine (IDU), 5-trifluoromethyl-deoxyuridine (TFT), and [E]-5-(2-bromovinyl)-deoxyuridine (BVDU).
- To assess the relationship between the concentration of these agents and the induction of sister chromatid exchange (SCE) in human cells.
- To provide data on the safety profile of these anti-herpes agents at therapeutic concentrations.
Main Methods:
- Human lymphocytes and fibroblasts were exposed to varying concentrations of IDU, TFT, and BVDU.
- The rate of sister chromatid exchange (SCE) was measured in treated cells as an indicator of genotoxicity.
- Comparative analysis of SCE rates was performed for each agent and concentration.
Main Results:
- 5-trifluoromethyl-deoxyuridine (TFT) significantly increased the rate of sister chromatid exchange (SCE) at a concentration of 0.5 mg/l.
- 5-iodo-deoxyuridine (IDU) and [E]-5-(2-bromovinyl)-deoxyuridine (BVDU) did not induce significant SCE except at a high concentration of 50 mg/l.
- TFT induced SCE at its minimal antiviral concentration, whereas BVDU did not induce SCE at therapeutic concentrations.
Conclusions:
- TFT exhibits mutagenic potential at concentrations relevant to its antiviral activity, suggesting caution in its use.
- BVDU appears safer at therapeutic concentrations, showing no significant mutagenic effects.
- The study highlights the differential genotoxic profiles of anti-herpes agents, emphasizing the importance of individualized safety assessments.