Lohani Mohtashim, Yadav Santosh, Schiffmann Dietmar, Rahman Qamar
Industrial Toxicology Research Centre, Division of Fibre Toxicology, Post Box No. 80, M.G. Marg, Lucknow 226 001, India.
Toxicol Lett. 2003 Jun 5;143(1):45-50. doi: 10.1016/s0378-4274(03)00112-7.
It is well known that asbestos fibers induced genotoxicity is mediated by reactive oxygen species (ROS) and insufficient endogenous antioxidant protection. Asbestos exposure can result in ROS generation in two different ways: (a) by catalyzation of Fe(2+), which is present in asbestos fibers, and (b) via oxidative bursts during phagocytosis of the fibers. On the other hand, it has been discussed that the physical presence of the fibres may mechanically influence the normal segregation of chromosomes during mitosis resulting in the induction of micronuclei in late ana/telophase, and aneuploidy. Glutathione and the glutathione redox system protect cells from the oxidative damage after exposure to xenobiotics. Glutathione depletion occurs during oxidative stress conditions and it is observed that supplementation of a precursor of glutathione and other sulphur containing compounds results in reduced toxicity. In the present study, diallyl sulfide (DAS), a lipid soluble allyl sulphur compound present in fresh extracts of garlic was evaluated for its protective effects. The micronucleus (MN) assay was performed in human mesothelial cells (HMC) exposed to 1 microg/cm(2) of crocidolite and chrysotile. Simultaneously, the cells were treated with 5 and 10 microM DAS, incubated for 48 and 66 h. Asbestos fibers induced significant genetic damage in HMC. The assay revealed a significant reduction in MN induction after treatment of cells with 5 microM but not with 10 microM DAS in mesothelial cells. The study revealed that at appropriate concentrations DAS protects mesothlelial cells against asbestos induced genotoxicity.
众所周知,石棉纤维诱导的遗传毒性是由活性氧(ROS)介导的,且内源性抗氧化保护不足。接触石棉可通过两种不同方式导致ROS生成:(a)通过催化石棉纤维中存在的Fe(2+);(b)通过纤维吞噬过程中的氧化爆发。另一方面,有人讨论过纤维的物理存在可能会在有丝分裂期间机械地影响染色体的正常分离,从而导致在后期/末期诱导微核和非整倍体。谷胱甘肽和谷胱甘肽氧化还原系统可保护细胞免受接触外源性物质后的氧化损伤。在氧化应激条件下会发生谷胱甘肽耗竭,并且观察到补充谷胱甘肽前体和其他含硫化合物可降低毒性。在本研究中,评估了大蒜新鲜提取物中存在的脂溶性烯丙基硫化合物二烯丙基硫醚(DAS)的保护作用。在暴露于1微克/平方厘米青石棉和温石棉的人间皮细胞(HMC)中进行微核(MN)试验。同时,用5和10微摩尔/升DAS处理细胞,孵育48和66小时。石棉纤维在HMC中诱导了显著的遗传损伤。该试验显示,在用5微摩尔/升而非10微摩尔/升DAS处理间皮细胞后,MN诱导显著降低。该研究表明,在适当浓度下,DAS可保护间皮细胞免受石棉诱导的遗传毒性。