The effect of the antioxidant catalase on oestrogens, triiodothyronine, and noradrenaline in the Comet assay.
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.
Djelic
Ninoslav
N
Department of Biology, Faculty of Veterinary Medicine, University of Belgrade, Serbia.
Anderson
Diana
D
D000328:Adult; D000975:Antioxidants / Q000494:pharmacology*; D002374:Catalase / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D020552:Comet Assay; D004247:DNA / Q000187:drug effects; D004249:DNA Damage; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects* / Q000473:pathology; D009638:Norepinephrine / Q000378:metabolism* / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D014284:Triiodothyronine / Q000494:pharmacology*
D000975:Antioxidants; D004967:Estrogens; D017382:Reactive Oxygen Species; D014284:Triiodothyronine; D004247:DNA; D002374:Catalase; D009638:Norepinephrine