Djelic Ninoslav, Anderson Diana
Department of Biology, Faculty of Veterinary Medicine, University of Belgrade, Serbia.
Teratog Carcinog Mutagen. 2003;Suppl 2:69-81. doi: 10.1002/tcm.10084.
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.
甾体雌激素酚基团的代谢变化伴随着醌类和活性氧的产生,这是其诱变作用的基础。尽管非甾体激素及相关化合物的遗传毒性尚未得到充分研究,但其中一些也含有可能参与氧化还原循环的酚基团。因此,本研究的目的是使用彗星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)对人淋巴细胞可能的DNA损伤作用。在剂量反应研究后,选择产生明显DNA损伤作用且细胞活力良好的100 microM T3和550 microM NA剂量,与抗氧化剂过氧化氢酶一起进行进一步实验。由于清除酶过氧化氢酶降低了T3和NA的DNA损伤作用,可以得出结论,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的诱变作用机制意味着产生氧化应激以及随后活性氧和可能在其氧化还原循环过程中产生的活性激素衍生物对DNA造成的损伤。