Resveratrol, a naturally occurring polyphenol, induces sister chromatid exchanges in a Chinese hamster lung (CHL) cell line.
We tested the genotoxicity of 3,5,4'-trihydroxystilbene (resveratrol), a polyphenolic phytoalexin found in grapes, in a bacterial reverse mutation assay, in vitro chromosome aberration (CA) test, in vitro micronucleus (MN) test, and sister chromatid exchange (SCE) test. Resveratrol was negative in the strains we used in the bacterial reverse mutation assay (S. typhimurium TA98 and TA100 and E. coli WP2uvrA) in the absence and presence of a microsomal metabolizing system. It induced structural CAs at 2.5-20 microg/ml and showed weak aneuploidy induction in a Chinese hamster lung (CHL) cell line. It induced MN cells and polynuclear and karyorrhectic cells after 48h treatments in the in vitro MN test. In the SCE test, resveratrol caused a clear cell-cycle delay; at 10 microg/ml, the cell cycle took twice as long as it did in the control. Resveratrol induced SCEs dose-dependently at up to 10 microg/ml, at which it increased SCE six-fold, and the number was almost as large as mitomycin C, a strong SCE inducer. No second mitoses were observed at 20 microg/ml even after 54h. Cell cycle analysis by FACScan indicated that resveratrol caused S phase arrest, and 48h treatment induced apoptosis. Our results suggest that resveratrol may preferentially induce SCE but not CA, that is, it may cause S phase arrest only when SCEs are induced.
Matsuoka
A
A
Division of Genetics and Mutagenesis, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, 158-8501, Tokyo, Japan. matsuoka@nihs.go.jp
Furuta
A
A
Ozaki
M
M
Fukuhara
K
K
Miyata
N
N
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002869:Chromosome Aberrations; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D005419:Flavonoids; D008168:Lung / Q000166:cytology; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D010636:Phenols / Q000633:toxicity*; D011108:Polymers / Q000633:toxicity*; D059808:Polyphenols; D000077185:Resveratrol; D012854:Sister Chromatid Exchange; D013267:Stilbenes / Q000633:toxicity*
D005419:Flavonoids; D009153:Mutagens; D010636:Phenols; D011108:Polymers; D059808:Polyphenols; D013267:Stilbenes; D000077185:Resveratrol