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

Table 3

Examples from the literature of vitamins’ 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
Vitamin A	Enhanced the levels of 8-oxo-dG DNA damage but significantly inhibited M1dG formation especially after induction of M1dG by H2O2 or B[a]P; increased production of reactive oxygen species and formation of promutagenic DNA lesions	Lung epithelial cells	Beta-carotene (5 𝜇mol/L)	Similar	[159, 160]
	Caused oxidation of dG and cytotoxicity, giving rise to an almost complete cell death	Leukemia cells (HL-60)	Retinol (2 𝜇mol/L) and ascorbic acid (50 𝜇mol/L)	Similar	[161]
	Induced apoptosis by increasing apoptotic protein p53 and decreasing antiapoptotic Bcl-2 as well as nuclear ATM; also induced DNA fragmentation	Gastric cancer cells (AGS)	Beta-carotene (100 𝜇mol/L)	Higher	[162]
	DNA damage on HepG2 which was also concordant to increased apoptosis and necrosis of cells	Hepatocarcinoma cells (HepG2)	Beta-carotene (4 𝜇mol/L) and 8 𝜇mol/L)	Similar	[163, 164]
	Reduced levels of total DNA adducts and increased apoptosis levels in cells coexposed to benzo(a)pyrene and retinoic acid		Retinoic acid (1 𝜇mol/L)	Lower
Vitamin B7 (biotin)	Increased strand breaks and cellular response to strand breaks	T-lymphocyte cell line (Jurkat)	25×10^−6 𝜇mol/L and; 0.01 𝜇mol/L	Lower and higher	[75]
	Affects biotinylation of proteins, gene expression, and metabolism of interleukin-2; rates of proliferation and apoptosis were not affected by biotin status		25×10^−6 𝜇mol/L, 25×10^−5 𝜇mol/L and 0.01 𝜇mol/L	Lower and higher	[165]
Vitamin B9	Increased levels of excision repair and apoptosis	Lymphocytes	Folate (<2.3×10^−3 𝜇mol/L)	Lower	[166, 167]
	Decreased apoptosis and increased cell proliferation	Neural stem cells (NSCs)	Folic acid (8.4×10^3 𝜇mol/L)	Higher	[168, 169]
	High concentration accelerated growth; increased metabolic activity, proliferation, and apoptosis; decreased differentiation	Human colon cancer cells (HT29)	Folic acid (0.021 𝜇mol/L and 0.21 𝜇mol/L) with other micronutrients involved in folate-methionine cycle	Similar and higher	[56]
Vitamin B12	Reduced cell proliferation and increased differentiation	Neuroblastoma cells (NIE115)	Vitamin B12 (total absence)	Lower	[89]
	Chronic exposure inhibited neurotoxicity	Retina cells (primary cultures from fetal rats)	Methylcobalamin (1 𝜇mol/L)	Higher	[170]
	Absence is likely to result both in reduced cell proliferation and in cell death, as inhibition of DNA synthesis generally results in apoptosis	Human erythroleukemic (K562) and murine lymphoma (BW5147) cell lines	Cobalamin (total absence and; 3.7×10^−3 𝜇mol/L)	Lower and higher	[171]
	Physiological concentrations of AA were not toxic, while high concentrations of AA induced DNA strand breakage in a dose-dependent manner, whereas AA2P were not genotoxic	Human dermal fibroblasts (HDFs)	Ascorbic acid (AA) and ascorbic acid 2-Phosphate (AA2P) (total absence or 20, 100, and 500 𝜇mol/L)	Lower, similar, and higher	[172]
Vitamin C	Enhanced DNA-protein crosslinks and cytotoxicity	Chinese hamster cells (V79)	Ascorbic acid (1000 𝜇mol/L)	Higher	[173]
	Decreased number of 8-hydroxydeoxyguanosine adducts	Mouse keratinocyte cell line	Ascorbic acid (2,27 𝜇mol/L and 4,54 𝜇mol/L)	Lower	[174]
	Protective effect against DNA damage induced by X-ray treatment	Human lymphoblastoid cells (Raji)	Ascorbic acid (60 𝜇mol/L)	Similar	[175]
	Protective effect against DNA damage induced by H2O2 treatment	Raji cells	𝛼-Tocopherol (30 𝜇mol/L)	Similar	[175]
Vitamin E	Reduced DNA fragmentation and apoptotic body formation, possibly favoring DNA repair	African green monkey kidney (Vero), human colon carcinoma (Caco-2), and dysplastic oral keratinocyte (DOK) cells	Vitamin E (25 𝜇mol/L)	Similar	[176]
	Reduced apoptosis and autophagy	Cultured trophoblasts and villous explants obtained from human placentas at term	Vitamin E (50 𝜇mol/L) with vitamin C (50 𝜇mol/L)	Higher	[177]