Stem Cells and Toxins
1. Alcohol Consumption
Excessive alcohol consumption results in cognitive and behavioral impairments related to hippocampal structure and function. The hippocampus is the part of the brain related to the creation of new neurons (called neurogenesis) and excess alcohol reduces neurogenesis and learning and memory.
Geil CR, Hayes DM, McClain JA, Liput DJ, Marshal SA, Chen KY, Nixon K. Alcohol and adult hippocampal neurogenesis: promiscuous drug, wanton effects. Prog Neuropsychopharmacol Biol Psychiatry 2014; 54: 103-13. on-line reference
2. Cigarette smoke
Stem cells can persist throughout our lives, having the capacity for proliferation and differentiation. However, these cells are also potential targets for tobacco smoke. Tobacco smoke contains thousands of substances which can produce oxidative stress and hypoxia. It is strongly linked to cancer. The skin have various stem cell populations. Tobacco toxins can be delivered through the blood stream or externally through second-hand smoke. The skin, hair follicle and nail stem cells can be biomarkers for tobacco exposure.
Kolanko E, Czekaj P. Skin and dermal appendages stem cells exposure to tobacco smoke. Przegl Lek 2013; 70(10: 858-64. on-line reference
b. Cigarette smoke, DNA damage and telomere shortening
Embryonic stem cells are used to test chemicals and environmental contaminants, including cigarette smoke. Chronic exposure of mouse embryonic stem cells to high doses of cigarette smoke condensate increased DNA damage and cell programmed death (apoptosis). Exposure to chronic low doses resulted in DNA damage and shortening of the telomeres. Telomeres are caps at the end of the DNA and as the telomeres shorten, there is an increased risk of cancer.
Huang J, Okuka M, Lu W, Tsibris JC, McLean MP, Keefe DL, Liu L. Telomere shortening and DNA damage of embryonic stem cells induced by cigarette smoke. Reprod Toxicol 2013; 35:89-95. on-line reference
c. E-Cigarettes and Neurotoxicity
In this study, refill solutions for E-Cigarettes were tested on human embryonic stem cells, mouse neural stem cells, and human pulmonary fibroblasts. Products from one company were cytotoxic to the stem cells but not the fibroblasts. The cytoxicity was related to the chemicals used to flavor the fluids.
Bahl V, Lin S, Xu N, Davis B, Wang YH, Talbot P. Comparison of electronic cigarette refill fluid cytotoxicity using embryonic and adult models. Reprod Toxicol 2012; 34(4):529-37. on-line reference
3. Methylmercury and Neural Stem Cells
Neurobehavioral effects of methylmercury include altered motor function and learning and memory disabilities. Methylmercury can also induce depression-like behavior. The authors showed that very low levels of methylmercury can inhibit neuronal differentiation of neural stem cells to produce these neurobehavioral effects.
Johansson C, Castoldi AF, Onishchenko N, Manzo L, Vahter M, Ceccatelli S. Neurobehavioural and molecular changes induced by methylmercury exposure during development. Neurotox Res 2007; 11(3-4):241-60. on-line reference
4. Lead and Neurotoxicity
Undifferentiated adipose derived stem cells were more vulnerable to lead exposure at an early stage of differentiation into neural cells. At this stage, lead is neurotoxic to the neural cells.
Qasemian Lemraski M, Soodi M, Fakhr Taha M, Zarei MH, Jafarzade E. Study of lead-induced neurotoxicity in neural cells differentiated from adipose tissue-derived stem cells. Toxicol Mech Methods 2015; 25(2):128-35. on-line reference
5. Chemicals and Neurotoxicity
In the developing nervous system, less differentiated human umbilical cord blood derived neural stem cells were more sensitive to neurotoxicants that included cadmium chloride, methylmercury chloride, and chlorpyrifos, with sensitivity to L-glutamate having greater toxicity at later stages.
Buzanska L, Sypecka J, Nerini-Molteni S, Compagnoni A, Hogberg HT, del Torchio R, Domanska-Janik K, Zimmer J, Coeche S. A human stem cell-based model for identifying adverse effects of organic and inorganic chemicals on the developing nervous system. Stem Cells 2009; 27(10):2591-601. on-line reference
b. Neuroprogenitor Cells and Neurotoxic Chemicals
Six chemicals (ethylnitrosourea, hydroxyurea, 5-azacytidine, cytosine arabinoside, 6-mercaptopurine and etoposide) were shown to cause DNA damage, neural programmed death (apoptosis) and cell cycle arrest in neural progenitor cells in the developing brain of mice and rats.
Doi K. Mechanisms of neurotoxicity induced in the developing brain of mice and rats by DNA-damaging chemicals. J Toxicol Sci 2011; 36(6):695-712. on-line reference
6. Organophosphorus Compounds
Organophosphorus compounds are pesticides that inhibit acetylcholinesterase to kill off insects. Reductions in motor speed and latency have been reported in preschool children from agricultural communities that use organophosphorus compounds. Low levels of paroxon altered the expression of various genes related to chromatin assembly and nucleosome integrity. The authors conclude that low dosees can affect the initial stage of neurodifferentiation possibly due to a teratogenic effect.
Pamies D, Sogorb MA, Fabbri M, Gribaldo L, Collotta A, Scelfo B, Vilanova E, Harris G, Bal-Price A. Genomic and phenotypic alterations of the neuronal-like cells derived from human embryonal carcinoma sem cells (NT2) caused by exposure to organophosphorus compounds paraoxon and mipafox. Int J Mol Sci 2014;15(1):905-26. on-line reference
7. The Gulf War and Neurotoxicity
Impairments in mood and cognitive function are the key brain abnormalities observed in Gulf war illness, a chronic multisymptom health problem afflicting about 25% of veterans who served in the Persian Gulf War-1. The authors show that combined exposure to low doses of a nerve gas drug pyridostigmine bromide and the pesticides DEET and permethrin induced depressive- and anxiety-like behavior and spatial learning and memory dysfunction. Mild stress exacerbated the mood and cognitive dysfunction. There was also reduced neural stem cell activity, reduced neurogenesis and a partial loss of principal neurons.
Parihar VK, Hattiangady B, Shuai B, Shetty AK. Mood and memory deficits in a model of Gulf War illness are linked with reduced neurogenesis, partial neuron loss, and mild inflammation in the hippocampus. Neuropsychopharmacology 2013;38(12): 2348-62. on-line reference
8. Environmental Pollution
Exposure to ambient fine particulate matter air pollution (greater than 2.5 um) causes endothelial dysfunction (cells within the blood vessel walls) and increases the risk of cardiovascular disease. Endothelial progenitor cells contribute to postnatal endothelial repair and regeneration. In humans and mice, endothelial progenitor cells are reduced upon exposure to elevvated levels of particular matter (2.5 um). In this study, particular matter at or above 2.5um inhibited the mobilization of endothelial progenitor cells in the bone marrow, causing deficits in blood vessel repair and regeneration.
Haberzettl P, Lee J, Duggineni D, McCracken J, Bolanowski D, O'Toole TE, Bhatnagar A, Conklin DJ. Exposure to ambient air fine particulate matter prevents VEGF-induced mobilization of endothelial progrenitor cells from the bone marrow. Environ Health Perspect 2012; 130(6):848-56. on-line reference
b. Environmental Pollution, Mutations and DNA Damage
Particulate air pollution is widespread and we need to know more about the long-term health implications associated with this exposure. In this study, mice were exposed to ambient air near two steel mills and a major highway and compared to control mice breathing air particulate filtered ambient air. Mice exposed to the air pollution for 10 weeks showed a 1.6-fold increase in sperm stem cell mutations. With exposure from 3 to 10 weeks, the mice showed DNA strand breaks in the sperm possibly resulting from oxidative stress from the airborne pollutants. The authors state that increased germ-line DNA mutations may cause population-level changes in the genetic composition and disease. Changes in the DNA can have widespread repercussions in gene expression and genome stability.
Yauk C, Polyzos A, Rowan-Carroll A, Somers CM, Godschalk RW, Van Schooten FJ, Berndt ML, Pogribny IP, Koturbash I, Williams A, Douglas GR, Kovalchuk O. Germ-like mutations, DNA damage, and global hypermethylation in mice exposed to particulate air pollution in an urban/industrial location. Proc Natl Acad Sci USA 2008; 105(2): 605-10. on-line reference
9. Hydraulic Fracking
The process of fracking requires large volumes of water, chemicals, a large well pad (3-7 acres) and an extensive network of transmission pipelines. The flowback and produced waters that return to the surface during production are high in total dissolved solids that contain halides (including chloride, bromide, fluoride), strontium, barium and often naturally occurring radioactive materials.
Lampe DJ, Stolz JF. Current perspectives on unconventional shale gas extraction in the Appalachian Basin. J Environ Sci Health A Tox Hazard Subst Environ Eng. 2015; 50(5): 434-46. on-line reference
b. Passive air samplers were used in a rural community heavily affected by this natural gas extraction. Samplers were analyzed for 62 polycyclic aromatic hydrocarbons (PAH). PAH levels were highest when samplers were closest to the active wells. PAH levels closest to natural gas activity were significantly higher than previously reported for rural areas. PAHs were predominantly petrol related. This work suggests that natural gas extraction may be contributing significantly to PAHs in the air at levels that can produce the risk of cancer to those in the area.
Paulik LB, Donald CE, Smith BW, Tidwell LG, Hobbie KA, Kincl L, Haynes EN, Anderson KA. Impact of Natural Gas Extraction on PAH Levels in Ambient Air. Environ Sci Techol 2015; 49(8): 5203-10. on-line reference
10. Radiation
Various stem cells react to genotoxic stress, including ionizing radiation in various ways. The authors discuss how the stem cells respond to these stresses.
Sokolov M, Neumann R. Lessons learned about human stem cell responses to ionizing radiation exposures: a long road still ahead of us. Int J Mol Sci 2013;14(8):15695-723. on-line reference
