Effect of docosahexaenoic acid and furan fatty acids on cytokinesis block micronucleus cytome assay biomarkers in astrocytoma cell lines under conditions of oxidative stress.
Fatty acids from fish such as docosahexaenoic acid (DHA) are associated with improved brain function, whereas furan fatty acids (FFAs) also found in fish oil at low levels (1%) are thought to have antioxidant properties. Understanding their effects in astrocytes is important as these cells are responsible for maintaining healthy neurons via lipid homeostasis and distribution within the brain, and their decline with aging is a possible cause of dementia. We investigated the cytotoxic and genotoxic effects of DHA and FFA using the cytokinesis-block micronucleus cytome assay in in vitro cultures of U87MG (APOE ɛ3/ɛ3) and U118MG (APOE ɛ2/ɛ4) astrocytoma cell lines with and without a hydrogen peroxide (H2O2, 100 µM) challenge. U118MG was found to be more sensitive to the cytostatic, cytotoxic (i.e., apoptosis), and DNA damaging effects [micronuclei (MNi), nucleoplasmic bridges (NPBs), and nuclear buds (NBUDs)] of H2O2 (P < 0.01 and P < 0.001) when compared with U87MG. DHA at 100 µg/mL significantly affected cytostasis (P < 0.05) and increased DNA damage in the form of NPBs and MNi (P < 0.05) in both cell lines, whereas it decreased necrosis (P = 0.0251) in U87MG. Significant DHA-H2O2 interactions were observed for decreased necrosis (P = 0.0033) and DNA damage biomarkers (P < 0.0001) in the U87MG cell line and increased cytostasis (P < 0.0001) in the U118MG cell line. The effects of FFA also varied between the cell lines, with significant effects observed in decreased cytostasis (P = 0.0022) in the U87MG cell line, whereas increasing cytostasis (P = 0.0144) in the U118MG cell line. Overall, FFA exerted minimal effects on DNA damage biomarkers.
Department of Physiology, School of Medical Sciences, University of Adelaide, Adelaide, Australia; Nutrigenomics and Neurodegenerative Disease Prevention, Preventative Health Flagship, CSIRO, Animal, Food and Health Sciences, Adelaide, Australia.
Ann
A
Chua
Philip
P
Thomas
Chakra
C
Wijesundera
Peter
P
Clifton
Michael
M
Fenech
D001057:Apolipoproteins E / Q000235:genetics; D017209:Apoptosis / Q000187:drug effects; D001253:Astrocytes / Q000187:drug effects*; D001254:Astrocytoma / Q000473:pathology; D015415:Biomarkers; D001932:Brain Neoplasms / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival; D048749:Cytokinesis / Q000187:drug effects; D004249:DNA Damage; D004281:Docosahexaenoic Acids / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D005227:Fatty Acids / Q000737:chemistry*; D005395:Fish Oils; D005663:Furans / Q000737:chemistry; D005838:Genotype; D006801:Humans; D006861:Hydrogen Peroxide / Q000737:chemistry; D008214:Lymphocytes / Q000187:drug effects; D015162:Micronucleus Tests; D009336:Necrosis; D018384:Oxidative Stress
D001057:Apolipoproteins E; D015415:Biomarkers; D005227:Fatty Acids; D005395:Fish Oils; D005663:Furans; D004281:Docosahexaenoic Acids; D006861:Hydrogen Peroxide
DNA damage; astrocytes; docosahexaenoic acid; furan fatty acid; micronuclei; oxidative stress