The Influence of Micronutrients in Cell Culture: A Reflection on Viability and Genomic Stability

Table 4

Examples from the literature of minerals’ effects in cell culture and on genomic stability.

Micronutrient	Main effects on cell viability and genomic stability	Cell type	Additional information regarding the form and concentration of the micronutrient evaluated	Status in relation to physiological concentration	References
	Increased cytotoxicity and ROS formation	HepG2	50, 100, 150, and 200 𝜇mol/L	Higher	[184]
Copper	Reduced mitochondrial activity and cell viability and increased DNA damage	Chinese hamster ovary cells (CHO-K1)	24.55, 35.40, 48.31, 89.23, 116.77, 170.75, 339.45, and 450.35 𝜇mol/L	Higher	[185]
	Increased the DNA damage in a dose-dependent manner and also reduced rates of DNA synthesis and histone acetylation	Leukemia cells (HL-60)	Total absence, 10, 20, 50, 100 and 200 𝜇mol/L	Lower, Similar, and Higher	[186]
	Inhibited DNA synthesis in proliferative cells	Human lymphocytes	Iron suiphate (22.38, 44.76, and 89.52 𝜇mol/L)	Similar and Higher	[187]
Iron	Possibly accelerated aging process and death at concentrations >10 𝜇mol/L, whereas 5 𝜇mol/L increased protein content	Cerebellar granule cells	Ferric nitrilotriacetate (5, 10, 15, 20, and 40 𝜇mol/L are shown	Lower, Similar, and Higher	[188]
	Genotoxic effects	Primary nontransformed colon cells and preneoplastic colon adenoma cell line (LT97)	Ferric nitrilotriacetate (10, 100, 250, 500, and 1000 𝜇mol/L)	Lower and Higher	[189]
	Inhibited cell proliferation and promoted endothelial dysfunction by generating proinflammatory, prothrombotic, and proatherogenic environment	Human endothelial cells	Magnesium sulphate (100, 500, and 1000 𝜇mol/L)	Lower and Higher	[190]
	Inhibited growth more drastically in normal than in transformed cells and altered cell-cycle progression	Normal (HC11) and transformed (MCF-7) breast epithelial cell lines	Total absence, 10, 30, 50, 100, 300, and 500 𝜇mol/L	Lower	[191]
Magnesium	Inadequate concentration accelerated cell senescence	Normal human fibroblasts (IMR-90)	100, 400, and 800 𝜇mol/L	Lower and Similar	[192]
	Incision repair completely inhibited in absence of Mg^2+ as well as at very high concentrations, whereas optimal concentrations essential in all steps of NER	Human lymphoblastoid (AHH1) and clonal human epithelial adenocarcinoma (HeLa S3) cell lines	400 and 800 𝜇mol/L	Lower and Similar	[193]
Selenium	Methylseleninic acid, L-selenocysteine, selenodiglutathione, or selenite-induced cell death in micromolar concentrations, whereas selenomethionine or ebselen was not toxic within the concentration range tested	HepG2, human hepatoma cell line (Huh-7), and mouse hepatoma (Hepa 1-6)	Sodium selenite, L- or DL-selenocysteine, selenodiglutathione, selenomethyl-selenocysteine, sodium selenate, L- or DL-selenomethionine, methylseleninic acid, ebselen, selenomethionine, and selenodiglutathione; (0.1×10^−3 to 1000 𝜇mol/L)	Lower, Similar and Higher	[194]
	Induces G1-cell cycle arrest and apoptosis via multiple signaling pathways, which may play a key role in methylselenol-induced inhibition of cancer cell proliferation and tumor cell invasion	Human sarcoma cell line (HT1080)	Seleno-L-methionine (SeMet) (total absence, 1.25, 2.5, and 5 𝜇mol/L)	Lower	[195]
	Decrease in cell damage and protection against oxidative stress	HepG2 cells	Selenium methylselenocysteine (0.01, 0.1, 1, and 10 𝜇mol/L)	Lower and Similar	[196]
			Selenium methylselenocysteine (1 𝜇mol/L)	Lower	[197]
	Increased oxidative DNA damage; disrupted p53, NF𝜅B, and AP1 DNA binding; decreased DNA repair	Rat glioma cell line (C-6)	Zn sulfate and Zn carnosine (4.0 𝜇mol/L)	Lower	[198]
Zinc	Decreased cell growth and viability, increased DNA SB and cytotoxicity in Zn-depleted cultures as well as at concentrations of 32 and 100 𝜇M; reduced genomic damage in cultures supplemented with 4 or 16 𝜇M	Human lymphoblastoid cell line (WIL2-NS)	Zn sulfate and Zn carnosine (total absence, 0.4, 4.0, 16.0, 32.0, and 100.0 𝜇mol/L)	Lower, Similar, and Higher	[199]
	Decreased cell viability in Zn-depleted cultures (0 𝜇M) as well as at concentrations of 32 and 100 𝜇M for both Zn compounds and increased DNA SB, apoptotic, and necrotic cells in Zn-depleted cultures	Primary human oral keratinocyte cell line (HOK)			[200]