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.
Matsuoka
Atsuko
A
Division of Medical Devices, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan. matsuoka@nihs.go.jp
Lundin
Cecilia
C
Johansson
Fredrik
F
Sahlin
Margareta
M
Fukuhara
Kiyoshi
K
Sjöberg
Britt-Marie
BM
Jenssen
Dag
D
Onfelt
Agneta
A
D000477:Alkylating Agents / Q000633:toxicity; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D003434:Crossing Over, Genetic / Q000187:drug effects*; D004261:DNA Replication; D004791:Enzyme Inhibitors / Q000633:toxicity; D006918:Hydroxyurea / Q000633:toxicity; D016685:Mitomycin / Q000633:toxicity; D021122:Protein Subunits / Q000187:drug effects; D000077185:Resveratrol; D012264:Ribonucleotide Reductases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000187:drug effects; D012854:Sister Chromatid Exchange; D013267:Stilbenes / Q000633:toxicity; D013329:Structure-Activity Relationship; D013997:Time Factors
C484543:3-hydroxystilbene; D000477:Alkylating Agents; D004791:Enzyme Inhibitors; D021122:Protein Subunits; D013267:Stilbenes; C064297:4-hydroxystilbene; D016685:Mitomycin; D012264:Ribonucleotide Reductases; D000077185:Resveratrol; D006918:Hydroxyurea