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Abstract
Ämnesord
Stäng
- We conducted the recombination and sister chromatid exchange (SCE) assays with five chemicals (hydroxyurea (HU), resveratrol, 4-hydroxy-trans-stilbene, 3-hydroxy-trans-stilbene, and mitomycin C) in Chinese hamster cell line SPD8/V79 to confirm directly that SCE is a result of homologous recombination (HR). SPD8 has a partial duplication in exon 7 of the endogenous hprt gene and can revert to wild type by homologous recombination. All chemicals were positive in both assays except for 3-hydroxy-trans-stilbene, which was negative in both. HU, resveratrol, and 4-hydroxy-trans-stilbene were scavengers of the tyrosyl free radical of the R2 subunit of mammalian ribonucleotide reductase. Tyrosyl free radical scavengers disturb normal DNA replication, causing replication fork arrest. Mitomycin C is a DNA cross-linking agent that also causes replication fork arrest. The present study suggests that replication fork arrest, which is similar to the early phases of HR, leads to a high frequency of recombination, resulting in SCEs. The findings show that SCE may be mediated by HR.
Nyckelord
- Alkylating Agents/toxicity
- Animals
- CHO Cells
- Cricetinae
- Cricetulus
- Crossing Over; Genetic/*drug effects
- DNA Replication
- Enzyme Inhibitors/toxicity
- Hydroxyurea/toxicity
- Mitomycin/toxicity
- Protein Subunits/drug effects
- Ribonucleotide Reductases/*antagonists & inhibitors/chemistry/drug effects
- Sister Chromatid Exchange
- Stilbenes/toxicity
- Structure-Activity Relationship
- Time Factors
Publikations- och innehållstyp
- vet (ämneskategori)
- art (ämneskategori)