Enhancing effects of cinoxate and methyl sinapate on the frequencies of sister-chromatid exchanges and chromosome aberrations in cultured mammalian cells.
Sister-chromatid exchanges (SCEs) induced by mitomycin C (MMC), 4-nitroquinoline-1-oxide (4NQO) or UV-light in cultured Chinese hamster ovary cells (CHO K-1 cells) were enhanced by cinoxate (2-ethoxyethyl p-methoxycinnamate) or methyl sinapate (methyl 3,5-dimethoxy 4-hydroxycinnamate). Both substances are cinnamate derivatives and cinoxate is commonly used as a cosmetic UV absorber. Methyl sinapate also increased the frequency of cells with chromosome aberrations in the CHO K-1 cells treated with MMC, 4NQO or UV. These increasing effects of methyl sinapate were critical in the G1 phase of the cell cycle and the decline of the frequencies of UV-induced SCEs and chromosome aberrations during liquid holding was not seen in the presence of methyl sinapate. Both compounds were, however, ineffective in cells treated with X-rays. In cells from a normal human embryo and from a xeroderma pigmentosum (XP) patient, MMC-induced SCEs were also increased by the post-treatment with methyl sinapate. The SCE frequencies in UV-irradiated normal human cells were elevated by methyl sinapate, but no SCE-enhancing effects were observed in UV-irradiated XP cells. Our results suggest that the test substances inhibit DNA excision repair and that the increase in the amount of unrepaired DNA damage might cause the enhancement of induced SCEs and chromosome aberrations.
Shimoi
K
K
Laboratory of Health Science, School of Pharmaceutical Sciences, University of Shizuoka, Japan.
Nakamura
Y
Y
Noro
T
T
Tomita
I
I
Sasaki
Y F
YF
Imanishi
H
H
Matsumoto
K
K
Shirasu
Y
Y
D015112:4-Nitroquinoline-1-oxide / Q000633:toxicity; D000818:Animals; D002460:Cell Line; D002869:Chromosome Aberrations; D002934:Cinnamates / Q000494:pharmacology*; D006224:Cricetinae; D004260:DNA Repair / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D016685:Mitomycin; D008937:Mitomycins / Q000633:toxicity; D009154:Mutation / Q000187:drug effects* / Q000528:radiation effects; D012854:Sister Chromatid Exchange / Q000187:drug effects; D014466:Ultraviolet Rays; D014983:Xeroderma Pigmentosum
D002934:Cinnamates; D008937:Mitomycins; C006605:antithiamine factor; D016685:Mitomycin; C018952:cinoxate; D015112:4-Nitroquinoline-1-oxide