Genotoxicity And Cytotoxicity Of Acrylamide

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Introduction

Genotoxicity
Genotoxicity is the ability of chemicals to cause damage to genetic material leading to mutations in genetic makeup (Klaunig & Rice, 2009). The mutations can eventually cause abnormalities in organisms in contact with the genotoxic material (Adewale et al., 2015). Such materials damage the genetic information in the cells which eventually leads to the development of cancerous properties.
One should not confuse genotoxicity with mutagenicity; all mutagenic chemicals are genotoxic, but not all genotoxic chemicals are mutagenic. With genotoxicity, one can expect direct and indirect effects on DNA including direct DNA damage, mutation induction, and mistimed event activation. Such impacts lead to heritable and direct changes that may be passed to future generations of cells.
Genotoxicity is induced by radiation and different chemical substances based on their resultant effects on the organism. Generally, genotoxins may be categorized into carcinogens, mutagens, and teratogens (Klaunig & Rice, 2009). Carcinogens eventually lead to cancer, while mutagens and teratogens cause mutations and birth defects respectively.
In terms of their mechanisms, genotoxic substances cause damage by interacting with the structure and sequence of DNA. One good example is where chromium interacts with DNA culminating in DNA lesions that cause cancer. In its high-valent oxidation state, chromium should not be placed dangerously close to organisms since it interacts with DNA resulting in cancer.

Genotoxic Agents in General
In general, genotoxic agents are noted to be mutagenic or carcinogenic to humans when they are ingested or inhaled. They also affect organisms when they penetrate the skin. Genotoxic agents can include radiation and chemical elements (Adewale et al., 2015). They are broadly categorized into carcinogens, mutagens, and teratogens.
Carcinogens can cause cancer in humans through their interaction with DNA. Such substances may be natural, including chemicals such as aflatoxin, produced by fungus and found in grains (Klaunig & Rice, 2009). Manmade substances also constitute carcinogens such as tobacco smoke and asbestos. All these substances negatively affect human DNA by inducing genetic mutations.
On the other hand, mutagens increase the frequency of mutations above the natural level leading to permanent changes in genetic material. It can result from a chemical or physical material that causes permanent changes to DNA. Good examples of mutagens include x-rays, UV radiation, chemicals, and radioactive substances.
Teratogens cause physical or functional defects in babies. Such substances include elements that a mother is exposed to during pregnancy. Some common substances may include street drugs, bacteria & viruses, medicines, toxic chemicals, and alcohol.

Acrylamide as a Genotoxic Agent
Acrylamide is a genotoxic substance, especially to humans where exposure can highly influence DNA (Blasiak et. al, 2004). It is an organic compound, a white, solid, and soluble chemical with the formula C3H5NO. In industrial chemistry, it is used to make polyacrylamides necessary for the creation of plastics, textiles, cosmetics, paper, and pulp.

Acrylamide and its genotoxicity were discovered in the 2000s when scientists noted that high amounts of the substance are developed by cooking different foods above 120°C in terms of temperature. The amount of the chemical present in cooked food is influenced by the temperature of cooking and duration of exposure. A study found that subjects eating high-temperature-prepared foods accumulate 0.5mg/kg of the substance daily based on their weight (Celik et al., 2018). More recent studies show 0.36μg/kg for men and 0.27μg/kg for women among the Dutch population (Celik et al., 2018).
As a genotoxic agent, acrylamide influences the cell DNA resulting in several consequences for the affected. First, it reduces viability and cell proliferation. There is a significant reduction in cell viability as discovered by Celik et al. (2018) and it has a negative proliferative effect on cells. Acrylamide also causes DNA fractures as confirmed through the FISH technique in the article by Celik et al. (2018).
The chemical also results in oxidative stress where the antioxidant/ oxidant balance is negatively affected. Such an effect is in the favor of oxidants as SORs increase in cells. In this condition, gene mutation, xenobiotic damage, and cancer development destroy cells.

Cytotoxicity
In general, toxicity is the property of a substance of being poisonous depending on the dosage. Toxicity is a more general term, but cytotoxicity defines how toxic a substance can become to human cells (Celik et al., 2018). Cytotoxic compounds can cause cell damage or even death. Some elements can be more toxic than others and doctors aim to understand every chemical’s cytotoxicity to determine how fatal or harmful it is to humans.
Some common compounds that are known to be cytotoxic include venoms and chemotherapy drugs. One common approach to measuring the cytotoxicity of a compound is by taking the ATP measure of the compound. Doctors or scientists can use protease markers or vital dyes to conduct such tests. It is also common for cytotoxicity to be underestimated since membrane integrity is compromised later in the cytotoxic process.
In a bioassay to understand the level of cytotoxicity, two classes of molecules can be used. They include vital dyes like trypan blue and DNA-binding dyes (Klaunig & Rice, 2009). Such substances cannot go through viable cells but can enter compromised cell membranes. The other class includes the cell markers that can leak out of an affected cell.
One area where cytotoxicity greatly applies is in cancer research and the development of chemo drugs. Doctors and scientists need to understand the cytotoxic effects of a drug on a human cell for effective treatment. It is also essential to understand any unintended effects on health cells for effective treatment.

Cytotoxic Agents in General
There are different types of cytotoxic agents including chemotherapy drugs and venoms as well as other elements. First, chemotherapy drugs are cytotoxic agents because of the effects they have on cancer cells. Such agents work by interrupting cells at various stages in the growth cycle.
Cytotoxic drugs are likely to affect rapidly growing cells such as cancer cells, bone marrow, and hair follicles as well as stomach & intestine linings. Some of these cytotoxic chemotherapy agents include alkylating agents, antimetabolites, and anti-tumor antibiotics. Another class of cytotoxic agents includes the cytotoxic venoms that highly affect human cells regardless of how they are ingested into the body.
Venoms produced by spiders, cobras, and vipers are cytotoxic agents. The most dangerous ones are known to cause death when injected into the human body. The substances interact with the body at the cellular level poisoning the cell and interrupting healthy cell activities. In extreme circumstances, cytotoxic compounds released by spiders and snakes cause death in humans.

Acrylamide as A Cytotoxic Agent
Acrylamide results in heat-treated foods especially carbohydrates such as bread and breakfast cereals (Aboubakr, 2019). Acrylamide increases as foods are subjected to heat for longer periods where the Millard reaction is a vital factor (Chen et al., 2013). It is also known that acrylamide may induce heritable mutations and carcinogenesis in humans.
In terms of its cytotoxicity, acrylamide-led cytotoxicity is connected to oxidative stress. Its cytotoxic properties emerge as the chemical affects the cellular redox status. Impacts on the cellular redox status might lead to the creation/ generation of reactive oxygen species (ROS) (Chen et al., 2013). ROS ultimately causes cytotoxic effects in humans.
As a manmade chemical or substance resulting from the cooking process, scientists need to consider strategies such as antioxidants to reduce acrylamide-induced cytotoxicity (Kahkeshani et al., & Abdollahi, 2014). In some cases, nutritional extracts from herbal plants can help reduce this cytotoxicity (Chen et al., 2013). This is important to ensure that the cytotoxicity of acrylamide does not cause carcinogenic effects to humans.

Acrylamide Properties
It is important to reflect on the properties of acrylamide to understand it for a better understanding of its genotoxicity and cytotoxicity. First, this substance is organic and it has the formula C3H5NO (Klaunig & Rice, 2009). It means that the chemical is a vinyl-substituted primary amide denoted by the formula CONH2 mostly created in the industries as a necessity for the development of polyacrylamides.

Acrylamide, in terms of its physical properties, is a white, soluble, and odorless solid used mostly in the chemical industries. It is developed for the creation of things like plastics, textiles, cosmetics, paper, and pulp needed for industrial purposes (Klaunig & Rice, 2009). It is also used as a flocculating agent and thickener. Some of these are functions relevant in their use in mineral extraction, paper-making, and water purification.
Acrylamide is also developed when food is cooked at above 120°C for a lengthy period. Foods such as bread and cereals exposed to such heat for a long time are likely to develop acrylamide which affects consumers of such foods. It can have adverse effects because of its cytotoxicity and genotoxicity.

Asparagus Properties
Asparagus is a perennial flowering species of plants whose shoots are used as a vegetable. Its scientific name is Asparagus officinalis. It is a nutritious addition to any diet because it is a good source of vitamins (A, C, & K), folate, and fiber (“Asparagus OFFICINALIS (Asparagus),” 2006). Eating this plant also has some additional benefits that may include reduced blood pressure, better digestion, and weight loss.
In terms of its nutrition content, 100g of asparagus has 0.1g fat, 2mg sodium, 202 mg of potassium, 3.9g of carbohydrate, and 2.2 g of protein in addition to vitamins, iron, and magnesium (Benson, 1999). These nutrient values are based on a typical 2000 calorie diet for adults, but daily values may vary depending on the energy needs of individuals.
It is also notable that asparagus is a good source of antioxidants; compounds that protect the cell from harm due to oxidative stress and free radicals. Its antioxidants include vitamins C and E as well as glutathione and flavonoids. Oxidative stress contributes to cancer, chronic inflammation, and aging (Kahkeshani et al., & Abdollahi, 2014). The antiviral, anticancer, and anti-inflammatory properties of asparagus help protect people from the above conditions.

Asparagus Treatment
In the recent past, there has been increasing use and studies about asparagus treatments and how such treatments can benefit people. In the above section, the properties of asparagus have been evaluated showing that it is a highly nutritious and beneficial plant for human consumption. It helps with cancer, chronic inflammation, and aging in humans. In addition, as a good source of fiber, it improves digestive health and lowers the risk of heart ailments, high blood sugars, and high blood pressure (“Asparagus OFFICINALIS (Asparagus),” 2006).
One example of treatment that is being experimented on today is the use of asparagus for the treatment of kidney stones. Steamed asparagus has been noted to help flush out kidney stones in humans because it is a mild diuretic. One can consume a half-pound of steamed asparagus or blend 6 to 8 ounces of asparagus and consume it as a smoothie to flush out kidney stones.
There is also increasing and conflicting ideas whether asparagus can help cure cancer especially prostate cancer. However, there seems to be no concrete evidence that asparagus can cure cancer. The best way to use asparagus is to eat it as a nutritious plant whose properties can help reduce the possibility of cancer, chronic inflammation, and aging as research about this plant and its benefits continues.

References
Aboubakr, M. (2019). Neuroprotective effects of clove oil in Acrylamide induced neurotoxicity in rats. Pakistan Veterinary Journal, 39(01), 111-115. doi:10.29261/pakvetj/2018.117
Adewale, O. O., Brimson, J. M., Odunola, O. A., Gbadegesin, M. A., Owumi, S. E., Isidoro, C., & Tencomnao, T. (2015). The potential for plant derivatives against Acrylamide neurotoxicity. Phytotherapy Research, 29(7), 978-985. doi:10.1002/ptr.5353
Asparagus OFFICINALIS (Asparagus). (2006). Vegetable Diseases, 129-136. doi:10.1201/b15147-22
Asparagus sprengeri asparagus. (2007). A Guide to Poisonous House and Garden Plants, 91-91. doi:10.1201/b16160-19
Benson, B. L. (1999). 9th international asparagus symposium.
Blasiak, J., Gloc, E., Wozniak, K., & Czechowska, A. (2004). Genotoxicity of acrylamide in human lymphocytes. Chemico-Biological Interactions, 149(2-3), 137-149. doi:10.1016/j.cbi.2004.08.002
Celik, F. S., Cora, T., & Yigin, A. K. (2018). Investigation of genotoxic and cytotoxic effects of acrylamide in HEK293 cell line. Journal of Cancer Prevention & Current Research, 9(5). doi:10.15406/jcpcr.2018.09.00365
Chen, W., Feng, L., Shen, Y., Su, H., Li, Y., Zhuang, J., … Zheng, X. (2013). Myricitrin inhibits acrylamide-mediated cytotoxicity in human caco-2 cells by preventing oxidative stress. BioMed Research International, 2013, 1-7. doi:10.1155/2013/724183
Kahkeshani, N., Saeidnia, S., & Abdollahi, M. (2014). Role of antioxidants and phytochemicals on acrylamide mitigation from food and reducing its toxicity. Journal of Food Science and Technology. doi:10.1007/s13197-014-1558-5
Klaunig, J., & Rice, J. (2009). Genotoxicity and carcinogenicity of acrylamide. Toxicology Letters, 189, S41. doi:10.1016/j.toxlet.2009.06.130

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