Stammati A, Bonsi P, Zucco F, Moezelaar R, Alakomi H L, von Wright A
Laboratorio TCE, Istituto Superiore di Sanità, Rome, Italy.
Food Chem Toxicol. 1999 Aug;37(8):813-23. doi: 10.1016/s0278-6915(99)00075-7.
In this study, several short-term microbial and mammalian in vitro assays were used to evaluate cytotoxicity and genotoxicity of four plant volatiles showing antifungal activity: cinnamaldehyde, carvacrol, thymol and S(+)-carvone. All inhibited viability and proliferation of Hep-2 cells in a dose-dependent manner. IC50 ranged from 0.3 mM (cinnamaldehyde) to 0.7 mM (thymol) in viability tests and from 0.2 mM (carvacrol) to 0.9 mM (carvone) in the proliferation test. The morphological analysis suggested an involvement of apoptosis in the cases of carvone, carvacrol and cinnamaldehyde. At nontoxic doses, carvacrol and thymol increased the number of revertants in the Ames test by 1.5-1.7 times, regardless of metabolic activation. In the SOS-chromotest, none of the four plant volatiles caused DNA damage at non-toxic doses. In the DNA repair test, a marked dose-dependent differential toxicity was observed with carvone and, to a lesser extent, with cinnamaldehyde, while with thymol and carvacrol, this effect was less pronounced. In conclusion, the considered in vitro cytotoxicity assays have shown to be sensitive enough to highlight a variety of toxic effects at the cellular level, which can be rather different between chemically closely related compounds, such as isomers.
在本研究中，使用了几种短期微生物和哺乳动物体外试验来评估四种具有抗真菌活性的植物挥发物的细胞毒性和遗传毒性：肉桂醛、香芹酚、百里香酚和S(+)-香芹酮。所有这些物质均以剂量依赖性方式抑制Hep-2细胞的活力和增殖。在活力测试中，IC50范围为0.3 mM（肉桂醛）至0.7 mM（百里香酚），在增殖测试中为0.2 mM（香芹酚）至0.9 mM（香芹酮）。形态学分析表明，香芹酮、香芹酚和肉桂醛的情况下存在凋亡现象。在无毒剂量下，无论有无代谢激活，香芹酚和百里香酚均可使Ames试验中的回复突变体数量增加1.5 - 1.7倍。在SOS-色测试中，四种植物挥发物在无毒剂量下均未引起DNA损伤。在DNA修复试验中，观察到香芹酮以及程度较轻的肉桂醛有明显的剂量依赖性差异毒性，而百里香酚和香芹酚的这种效应则不太明显。总之，所考虑的体外细胞毒性试验已证明足够灵敏，能够突出细胞水平上的多种毒性效应，这些效应在化学结构密切相关的化合物（如异构体）之间可能有很大差异。
