Effect of docosahexaenoic acid and furan fatty acids on cytokinesis block micronucleus cytome assay biomarkers in astrocytoma cell lines under conditions of oxidative stress

Abstract

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.

Epigenetic Regulation of Centromere Chromatin Stability by Dietary and Environmental Factors

“…For instance, in hepatocellular carcinoma, the presence of oxidative stress and inflammation leads to epigenetic instability that modifies the methylation status of DNA at different genetic loci, including tumor suppressor gene promoters, repetitive elements, and satellite DNA (84), which provides a probable link between metabolic status and the initiation of CIN. It has also been shown that under oxidative stress conditions, the addition of 1-10 mg DHA/mL to astrocyte cell culture (APOE 33/33 and 32/34 genotypes) was able to protect against H 2 O 2 genotoxic damage by decreasing the occurrence of miconuclei (85). Moreover, protein-energy malnutrition has been found to induce chromosomal aberrations (86)(87)(88), and this phenotype was rescued by ZnSO 4 supplementation (87).…”

Antimutagenicity and induction of antioxidant defense by flavonoid rich extract of Myrcia bella Cambess. in normal and tumor gastric cells

“…The present study demonstrated that the NUBD frequency after treatment with the MB extract in combination with DXR in a simultaneous experimental protocol in normal and tumor cells was higher compared to the control cells. One mechanism involved in NUBDs formation is gene amplification (Fenech et al, 2011) and/or removal of DNA repair complexes (Chua et al, 2014). Our results cannot identify which gene is amplified, but one hypothesis is that the overexpression of different genes may be related to increases in the NUBDs frequency, including CCND1 that had its expression increased approximately five-fold in both cell lines.…”

“…Evaluation of the oxidant activity using the CM-H 2 DCFA probe showed an oxidant effect of the MB extract only on tumor cells, which may be related to the mutagenic effect observed in these cells. Chua et al (2014) also demonstrated that the frequency of NUBDs increased with the oxidative stress induced by H 2 O 2 in an astrocytoma cell line. Antimutagenic effects were observed in both cell lines in the CBMN-cyt assays when the cells were treated with the MB extract plus DXR.…”