Kocaman Ayse Yavuz, Istifli Erman Salih, Büyükleyla Mehmet, Rencüzogullari Eyyüp, Topaktaş Mehmet
Department of Biology, Mustafa Kemal University, Turkey.
Toxicol Ind Health. 2013 Feb;29(1):23-37. doi: 10.1177/0748233712436640. Epub 2012 Feb 9.
4-Thujanol (sabinene hydrate), a bicyclic monoterpene alcohol, is found in the essential oils of many aromatic and medicinal plants and is widely used as a fragrance and flavouring agent in many different products. The aim of this study was to evaluate the protective effects of 4-thujanol against the genotoxic effects induced by mitomycin C (MMC) and cyclophosphamide (CP) in human lymphocytes, using the chromosome aberrations, sister chromatid exchanges, and micronucleus tests, in the absence and in the presence of S9 mix, respectively. The cells were treated with 0.25 µg/mL MMC and 28 µg/mL CP as alone and cotreated with 13 + 0.25, 26 + 0.25, and 52 + 0.25 µg/mL 4-thujanol + MMC and with 13 + 28, 26 + 28, and 52 + 28 µg/mL 4-thujanol + CP as a mixture. The present study showed that 4-thujanol was unable to reduce the genetic damage induced by MMC, in the absence of S9 mix. On the other hand, probably the metabolites of 4-thujanol act as an antagonist and markedly antagonize CP-induced genotoxicity, in the presence of S9 mix. In general, 4-thujanol + MMC and 4-thujanol + CP decreased the mitotic index, proliferation index and nuclear division index to the same extent or more than those of individual exposure of MMC or CP. In conclusion, 4-thujanol significantly reduced (p < 0.001) the genotoxic damage induced by CP but not MMC when compared with the respective positive control alone. We can suggest that 4-thujanol may improve the chemopreventive effects and may also reduce the harmful side effects of CP, which is widely used in chemotherapy against cancer, without reducing its antiproliferative activities.
4-松油醇（水合桧烯）是一种双环单萜醇，存在于许多芳香植物和药用植物的精油中，并在许多不同产品中广泛用作香料和调味剂。本研究的目的是分别在不存在和存在S9混合物的情况下，使用染色体畸变、姐妹染色单体交换和微核试验，评估4-松油醇对丝裂霉素C（MMC）和环磷酰胺（CP）诱导的人淋巴细胞遗传毒性的保护作用。细胞分别单独用0.25μg/mL MMC和28μg/mL CP处理，并分别与13 + 0.25、26 + 0.25和52 + 0.25μg/mL 4-松油醇+ MMC以及13 + 28、26 + 28和52 + 28μg/mL 4-松油醇+ CP混合处理。本研究表明，在不存在S9混合物的情况下，4-松油醇无法降低MMC诱导的遗传损伤。另一方面，在存在S9混合物的情况下，4-松油醇的代谢产物可能作为拮抗剂，显著拮抗CP诱导的遗传毒性。一般来说，4-松油醇+ MMC和4-松油醇+ CP使有丝分裂指数、增殖指数和核分裂指数降低的程度与单独暴露于MMC或CP时相同或更大。总之，与各自单独的阳性对照相比，4-松油醇显著降低了（p < 0.001）CP诱导的遗传毒性损伤，但对MMC诱导的遗传毒性损伤没有降低作用。我们可以认为，4-松油醇可能会提高化学预防效果，还可能降低CP的有害副作用，CP广泛用于癌症化疗，而不会降低其抗增殖活性。
