A Short Review on Carcinogenicity

Dhananjay D. Chaudhari, Karishma. P. Bhadane, Priyanka. V. Pawar

Ahinsa Institute of Pharmacy, Dondaicha, Shindkheda, Dhule, Maharashtra, India 425408.

*Corresponding Author E-mail: cdhananjay86@gmail.com

ABSTRACT:

Humans are exposed to a variety of different and persistent DNA-damaging agents, some of which have been identified as carcinogens. DNA damage can occur from exposure to exogenous agents, but damage from endogenous processes is more common. That is, epidemiological studies of migrant populations from low-cancer-risk areas to high-cancer-incidence countries suggest the role of environmental factors and/or lifestyle as important players in the etiology of cancer. As a result, it can be assumed that carcinogens found in the environment or our diet are to blame. Carcinogen exposure is associated with various forms of DNA damage, including single-strand breaks, double-strand breaks, chemical DNA cross-links, oxidative stress, and DNA-DNA or DNA-protein breaks. This review focuses on DNA damage caused by the following carcinogens: polycyclic aromatic hydrocarbons, heterocyclic aromatic amines, mycotoxins, ultraviolet light, ionizing radiation, aristolochic acid, nitrosamines, and particulate matter. In addition, we discuss several cancers for which molecular epidemiological evidence suggests that these agents are etiological risk factors. The complex role that carcinogens play in the pathophysiology of cancer development remains unclear, but DNA damage remains central to this process.

KEYWORDS: Bioactivation, Cancer, Carcinogens, DNA damage.

INTRODUCTION:

A carcinogen is any substance, radionuclide or radiation that induces carcinogenesis or cancer. This may be due to damage to the genome or disruption of cellular metabolic processes. Some radioactive substances are considered carcinogens, but their carcinogenic activity is related to radiation, such as gamma rays and emitted alpha particles. Common examples of non-radioactive carcinogens include asbestos, certain dioxins, and inhalation of tobacco smoke. Although many associate carcinogenicity with synthetic chemicals, it is likely to occur from both natural and synthetic materials. Carcinogens are not directly toxic; thus, their influence may be subtle.

Carcinogens, as mentioned above, are environmental agents that can contribute to the development of cancer. Carcinogens can be divided into two different types:

activation-dependent and activation-independent, and each nature affects their level and mode of action in promoting the development of cancer do not directly associate with cancer. Free carcinogens in tobacco products, such as ultraviolet rays or nitrosamines, have properties that allow them to interact directly with DNA and other cellular components causing damage. Among these, there is no metabolic activity or molecular changes required for movement, which complements the ability to be electrically excited, so it can interact with oxygen and nitrogen atoms in the cellular environment with a negative charge. This type of interaction causes the nucleotide base of the DNA to change, causing the genetic material to become disorganized. This mismatch is also responsible for the formation of DNA adducts, DNA segments that bind to carcinogens. Eventually, failure of DNA repair mechanisms will lead to DNA damage and cancer. A tumor is any disease that affects normal cells and does not undergo programmed cell death, such as dividing through mitosis. Carcinogens can damage cell DNA by changing cell metabolism or interrupting biological processes and causing uncontrolled, harmful division, increasing the risk of cancer. Normally, severe DNA damage causes programmed cell death, but if the programmed cell death pathway is damaged, the cell cannot turn itself into a cancer cell. There are many natural carcinogens. Aflatoxin B1, produced by the fungus Aspergillus flavus, which grows in stored grains, nuts, and soybean oil, is an example of a potent, naturally occurring microbial carcinogen. Some viruses, such as hepatitis B and human papillomavirus, have been shown to cause cancer in humans^1,2.

Types of Carcinogens:

Carcinogens exist in a range of indoor or outdoor environments. They include chemicals, viruses, medications, and pollutants. Some carcinogens are linked to specific types of cancer.

1. Home and Workplace Chemicals:

Many chemicals used in building material or products in the home or workplace may be carcinogenic. For example, formaldehyde is a carcinogen that’s used in building materials and a variety of furniture and household products. It’s commonly found in composite wood products (hardwood plywood, particleboard, and medium-density fiberboard) that emit chemicals into the room. You may hear this referred to as “off-gassing.” Formaldehyde is also a byproduct of lit cigarettes and smoking.

2. Medical Radiation:

Radiation exposure that occurs during certain diagnostic tests, such as computed tomography (CT scan), and radiation therapy used to treat cancer is carcinogenic.

For example, women who receive radiation therapy after a mastectomy, a procedure to remove a breast due to breast cancer, are at an increased risk of developing lung cancer due to the radiation that is delivered to the chest area. However, the risks of not getting such imaging or treatment when needed are often considered greater than those associated with medical radiation.

3. Viruses:

There are several viruses linked to cancer. These affect healthy cells’ genetic makeups and can make it more likely that they will turn into cancer.

4. Medications:

Some chemotherapy and hormonal therapy drugs can raise the risk of cancer. For example, chemotherapy drugs such as Ellence (epirubicin) and Cytoxan (cyclophosphamide), used for early stage breast cancer, can sometimes lead to leukemia. Oral contraceptive use may increase the risk of breast cancer or cervical cancer, but they may lower the risk of endometrial, ovarian, and colorectal cancers.

5. Pollution:

Both outdoor and indoor air may contain pollutants that are carcinogenic. Common outdoor air pollutants from industrial or power plants, engine exhaust, and fire smoke are strongly linked with lung cancer³.

Symptoms:

· Signs and symptoms caused by cancer vary depending on which part of the body is affected.

· Some common signs and symptoms associated with ovarian cysts include:

· resistance

· An area of palpable lump or thickening under the skin

· Changes in weight, including unplanned loss or gain

· Skin changes, such as yellow, dark, or red, ulcers that will not heal, or changes in moles.

· Changes in bowel or bladder habits

· Persistent cough or difficulty breathing, Difficulty exaggerating

· Shouting

· Persistent indigestion or discomfort after meals

· Persistent, unexplained muscle or joint pain

· Persistent, unexplained arguments or night sweats

· Bleeding or bruising that cannot be explained^5,6

Causes:

Carcinogenic. A carcinogen is any substance that can cause cancer. Identifying potential carcinogens is important because we can take specific steps to avoid or limit exposure to them. The US Department of Health and Human Services’ National Toxicology Program and the World Health Organization’s International Agency for Research on Cancer both use evidence-based approaches to catalog substances known or expected to be human carcinogens. Both use an evidence-based approach to catalog substances that are known or suspected to be human carcinogens. Until now, more than 500 substances have been identified as definite, probable, or possible carcinogens for humans. These include things like asbestos, car exhaust, processed meats or ultraviolet rays. Exposure to carcinogens does not necessarily mean that cancer will develop. The amount and duration of exposure, exposure to other environmental factors, and the individual’s genetic background influence whether a person is exposed to a carcinogen and ultimately develops cancer^6,7

Medical treatment and tests:

Some medical treatments and tests are carcinogenic because they increase the risk of cancer. Hormone-related medications, such as oral birth control and hormone replacement therapy (HRT), can increase the risk of certain cancers in women. Certain cancers and treatments such as chemotherapy and radiation are known to increase a patient’s risk of developing other cancers.

Medicines that suppress the immune system and treat inflammatory conditions such as Crohn’s disease and rheumatoid arthritis can increase the risk of cancer. These include Humira, Enbrel, Remicade, and prednisone.

In 2019, some pharmacists are recalling blood pressure and nausea drugs due to NDMA contamination. Blood pressure medications that have been discontinued include valsartan and losartan. After the valsartan recall, an independent pharmacy found NDMA in Zantac (ranitidine), and the manufacturer issued a recall.

Before you receive any medical treatment or medication, talk to your pharmacist or doctor about the risks and benefits of certain medications.⁸

CONCLUSION:

The Gen-Tox Carcinogen Database, a qualitative analysis of cancer, can accompany the quantitative analysis of cancer literature found by Peto et al. and gold etc. These studies and databases can be used to assess the ability of genetic toxicology and related bioassays to detect chemical carcinogens. In conclusion, the Gen-Tox Carcinogenesis Panel recommends that methods be explored to encourage the publication of data that clearly demonstrate the inactivity of chemicals when administered to experimental animals. It is also appreciated that the Gen-Tox Carcinogenic Database is updated periodically to include new assessments from IARC, NTP, and the Gen-Tox Carcinogenesis Panel.

REFERENCE:

1. https://en.m.wikipedia.org/wiki/Carcinogen

2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6195640/

3. https://www.verywellhealth.com/what-is-a-carcinogen-2249070

4. https://byjus.com/chemistry/carcinogenicity-and-toxicity/

5. https://www.mayoclinic.org/diseases-conditions/cancer/symptoms-causes/syc-20370588

6. https://gmoanswers.com/examples-international-agency-research-cancer-iarc-carcinogenic-classifications-infographic

7. https://www.genome.gov/geneticsglossary/Carcinogen#:~:text=

Carcinogens%20may%20occur%20naturally%20in,cell’s%20DN

A%20to%20produce%20mutations.

8. https://www.drugwatch.com/health/cancer/carcinogens/

Received on 01.12.2022 Modified on 05.02.2023

Asian J. Res. Pharm. Sci. 2023; 13(2):185-187.

DOI: 10.52711/2231-5659.2023.00032