Correlation of sister chromatid exchange formation through homologous recombination with ribonucleotide reductase inhibition.

• 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.

Keyword

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

Publication and Content Type

vet (subject category)

art (subject category)