The effect of the antioxidant catalase on oestrogens, triiodothyronine, and noradrenaline in the Comet assay.

Ninoslav Djelic, Diana Anderson
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引用次数: 43

Abstract

Metabolic changes in the phenolic groups of steroidal oestrogens accompanied by the generation of quinones and reactive oxygen species underlie their mutagenic effects. Although nonsteroidal hormones and related compounds have not been thoroughly investigated for genotoxicity, some of them also contain phenolic groups that could be involved in redox cycling. Therefore, the aim of the present study was to evaluate the possible DNA damaging effects of the thyroid hormone, triiodothyronine (T3), and the neurotransmitter, noradrenaline (NA), in human lymphocytes using the Comet assay. After dose-response investigations, doses of 100 microM T3 and 550 microM of NA, producing clear DNA damaging effects and good cell viability, were chosen for further experiments with the antioxidant, catalase. Since the scavenging enzyme catalase reduced the DNA damaging effects of T3 and NA, it can be concluded that T3 and NA induced DNA damage mainly via the production of reactive oxygen species. Therefore, the mechanism of mutagenic action of both steroidal hormones and nonsteroidal compounds, T3 and NA, imply the creation of oxidative stress and subsequent DNA damage with reactive oxygen species and, possibly, with reactive hormone derivatives created during their redox cycling.

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抗氧化过氧化氢酶对雌激素、三碘甲状腺原氨酸和去甲肾上腺素的影响。
甾体雌激素的酚类代谢变化伴随着醌和活性氧的产生,是其致突变作用的基础。虽然非甾体激素和相关化合物的遗传毒性尚未得到彻底的研究,但其中一些还含有可能参与氧化还原循环的酚类。因此,本研究的目的是利用Comet试验评估甲状腺激素三碘甲状腺原氨酸(T3)和神经递质去甲肾上腺素(NA)在人淋巴细胞中可能的DNA损伤作用。经过剂量-反应研究,选择100微米T3和550微米NA剂量,产生明显的DNA损伤作用和良好的细胞活力,进行抗氧化剂过氧化氢酶的进一步实验。由于清除酶过氧化氢酶降低了T3和NA对DNA的损伤作用,因此可以认为T3和NA主要通过产生活性氧诱导DNA损伤。因此,甾体激素和非甾体化合物(T3和NA)的致突变作用机制暗示了氧化应激和随后的DNA损伤与活性氧的产生有关,也可能与氧化还原循环过程中产生的反应性激素衍生物有关。
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