Overview of Toxic Compounds Causing Mutation and Disrupt

Introduction

Nowadays, there are various chemicals being exposed to human naturally or synthetically. It can be present in pharmaceutical products, cosmetics, pesticides and even foods. Few of the chemicals present in typical daily product may be cancer inducing chemicals that can be dangerous for human for long exposure periods. Cancer is characterized by the uncontrollable proliferation of cells and spreading of abnormal cells in human body system. It also may result in death without a proper treatment. Certain chemicals can cause mutation and disrupt the replication DNA in human by giving or stop certain signals in human. These types of chemicals are known to be toxic compounds. There are several types of toxic compounds which are teratogen, mutagen and carcinogen.

Definition and Explanation

Mutagenic

Mutagenic is a physical or chemical agents that can cause mutations to the DNA permanently and also may induce cancerous cells. According to Occupational Safety and Health Act (2017), mutagenic is also generally consider as genotoxic because it can alter the structure, information or segregation of DNA. Mutagen can be divided into chemical and physical mutagen.

Chemical mutagen

Chemical mutagen can be defined as compounds that increase the rate of mutation. It works by interact with the DNA and cause changes in the sequence in the DNA. It occurs by the process of deletion, addition or replacement of the DNA bases. When mutation presence in the DNA sequence, the protein synthesis will either prevented or it will produce a modified protein. As a result, it will cause disease and give different signal to the organ and cells. Example of chemical mutagens is alkylating agents and azides.

Base analogs

Base analogs mutagen is a chemical bases that able to disturb the replication system. it mimics the normal bases of purines and pyrimidines. This will leads to incorrect insertion of nucleotides in replication. As a result, it will change the base pairing and structural of the DNA. Examples of base analogs mutagen is 5-bromouracil because it can pair with either adenine or guanine. It shows that 5-bromouracil can imitate Thymine and added into the DNA by pairing with adenine or guanine. It is added in the DNA because of tautomerization. Due to that reason, the mispairing of the bases will eventually lead to the mutation. Other than that, base analogs mutagen may also prevent DNA synthesis by inhibiting certain production of enzymes.

Alkylators

Alkylators are the chemicals that can change the structure and pairing properties of DNA. It can modify the structure by addition of alkyl group in the structure base of DNA. Examples of alkylating agents are ethylmethanesulfonate (EMS) and nitrosoguanidine (NG). According to Griffiths, Miller, Suzuki, Lewontin, and Gelbart (2000), ethylmethanesulfonate will add oxygen at the position 6 of guanine that will resulting with an O-6-alkylguanine. As a result it will mispair with thymine and produce different base pairing in replication, at the same time induces mutation. Besides that, alkylating agents are also said to modify the dNTPs bases. This may cause a disruption in the DNA synthesis as it is the precursors for the process.

Physical mutagens

There are two types of physical mutagen which is the ionizing radiation and non-ionizing radiation. Ionizing radiation is the radiation with sufficient energy required to remove the bound electrons from an atom. This process will result in formation of excited molecules that can cause damage to DNA and also cellular components when exposed to human. Moreover, ionizing radiation is able to penetrate cells and cause mutation to human’s cell. Examples of ionizing radiations are x-rays, γ rays and α particle. It is highlighted by Lerner and Lerner (2003) that x-rays and γ rays have high penetration than other radiation. Because of that, it will cause an even energy distribution thus causing more severe damage. Meanwhile, example of non-ionizing radiation is UV radiation. UV radiation can also affect the DNA bases by producing lethal lesions in DNA which is pyrimidine dimmers. This dimer will block transcription and DNA replication process.

Meanwhile, teratogens are substances that can cause birth defects by injuring or attacking the fetus during pregnancy. Teratogens can be closely connected with embryotoxins which is poisonous to the development of fetus. The teratogenicity of an agents are depends on the capabilities of the compounds to penetrates the placents. Besides that, it can also induce the congenital malformation in infants during the fetus development. The severity of the defects is depending on the duration of exposure, amount of substance, the concentration of the substance and also the embryonic stage of the fetus. The most famous case in history of teratogens compounds would be the usage of thalidomide as nausea and morning sickness medicine. Throughout the years, there had been an increasing amount of newborn babies with malformation of limbs which called phocomelia. After a thorough research been conducted, it concluded that thalidomide is the main cause of phocomelia as it is a teratogen agent. Phocomelia is the shortening of the limbs by the reduced length of proximal elements and only leaving the distal elements. The thalidomide is a synthetic derivative of the glutamic acid and the parent molecule of thalidomide is said to be the compounds that are teratogens in human.

Furthermore, metabolic condition occurs to pregnant woman also consider as second category of teratogens. This is because with the abnormalities occur in the chemical process of the pregnant woman, it will significantly affected the development of the fetus. According to Tantibanchachai (2014), diabetes may cause neural tube, brain, and spinal cord defects by the excessive blood sugar level presence in the system of a pregnant lady. It shows that, teratogens agent can also be the diseases condition in a pregnant lady as well as the foreign compounds that people are ingested or exposed to. It is important that pregnant woman avoid in contact with teratogens substances. The first trimester of woman’s pregnancy is vital in the foetus development thus the mother should be extra cautious on what they eat as well as what chemicals that they are exposed towards. Teratogens agents include ethanol, mercury compounds, carbon disulfide and toluene. In addition to that, there are also common items that contain teratogens compound in its contents like alcohol, cigarettes and drugs. In addition to that, pregnant woman also need to ensure they are in good conditions and avoid any hazardous compounds.

Carcinogenic

Carcinogenic substances are commonly associated with the cause of cancer not only in humans but also animals. The process that causes cancer is called carcinogenesis. Carcinogenesis is a process of cancer formation from the normal cells. Carcinogen agents may be present naturally or synthetically. Carcinogens also able to accelerates cell division and automatically prevent cells repair mechanism to take action. Examples of substances that are carcinogens are benzene, vinyl chloride, formaldehyde dioxane and acrylamide. There are also common carcinogen agents like asbestos, cigarettes and also radon gas. With the exposure of these substances, human’s body may react by inducing carcinogenesis that will lead to cancer.

Carcinogens can be classified as genotoxic or nongenotxic. Genotoxins can cause cancer by directly damage or change the genetic materials of specific cells. Meanwhile, nongenotoxin affect the hormones and organic compounds that relating with the cell growth and indirectly cause cancer. Lee and coworkers (2013) stated that genotoxin agents may cause severe DNA damage like formation of cross-links between two helices, removal of DNA bases and cleavage of the DNA strands. All this condition may lead to mutation and indirectly cause cancer. Human Papilloma Virus or HPV is an example of biological carcinogen. This virus may cause cervical cancer and mostly affecting woman. HPV contain genes that may disrupt the cell division of the normal cell. As highlighted by Nickle and Barette-Ng (2016), HPV contain E6 and E7 genes that can cause an unsuppressed cell division by inhibiting the host cells tumor suppressing proteins. The virus will inhibit the signal produces by the protein and will cause uncontrolled cell division. However, it can be treated with proper treatments.

Conclusion

In conclusion, all these types of compounds can lead to severe diseases and may cause death. Precautions must take into accounts when handle these compounds. Despite being toxic, there are few of these chemicals existed in daily product thus as a consumer awareness is important.