Carcinogenicity

Carcinogenicity studies are used to identify a test article’s oncogenic potential in animals in order to assess the risk of cancer in people. Carcinogenicity testing is required for pharmaceutical substances that will be consistently provided for at least six months. A carcinogenicity study may be required for products that will be used regularly in an intermittent way.

In the late 1990s to early 2000s, carcinogenicity tests on rats indicated some indication that naphthalene could be carcinogenic. As a result of these findings, the International Agency for Research on Cancer has classified naphthalene as a chemical that may cause cancer in humans. This article will provide evidence on carcinogenicity and also on mutagenicity studies. 

What Is Carcinogenicity?

A carcinogen is any type of causative agent that changes the DNA sequence, especially the nitrogenous bases, or introduces disparity in mitotic cellular division. Out of the two impacts, it is the latter that prevails the most and causes cancers. Carcinogens can be divided into two types – natural and synthetic.

• Natural carcinogens occur in nature and, therefore, no one can eliminate their presence. For example, radioactive rays are carcinogenic, but one cannot eliminate them. The only form of safety is protection. 
• Synthetic carcinogens are man-made, like nicotine, asbestos, VOCs, and more. If the use of these harmful substances is mitigated, then it will be possible to reduce the chances of cancer. 

Cancer is defined as a disease wherein somatic cells (regular body cells) multiply uncontrollably. They do not follow the diploid cell division rule (2n multiplication). Carcinogens can increase cancer risk by altering cell functions or directly damaging DNA in cells, interacting with other biological processes and triggering uncontrolled, tumorigenic division, which can lead to tumour formation. Severe DNA damage generally results in planned cell death, but if this route is disturbed, the cell will be unable to protect itself from becoming a cancer cell.

Following the ingestion of a carcinogen through food, drink, smoking, etc., the body attempts to remove it through alterations within the body. These processes aim to render the carcinogen highly water-soluble, allowing it to be excreted from the body. These interactions, however, can sometimes turn a less deadly carcinogen into a more deadly carcinogen.

Because DNA is nucleophilic, soluble carbon electrophiles can induce cancer because DNA assaults them. Some alkenes, for example, are intoxicated by human enzymes, resulting in an electrophilic epoxide. DNA assaults the epoxide and becomes irreversibly entangled with it. The carcinogenicity of benzopyrene from tobacco smoke, aflatoxin, various aromatics, and mustard gas is due to this mechanism.

What Is Mutagenicity?

Mutagenicity is defined as the induction of transmissible alterations in the quantity or structure of a cell’s or organism’s genetic material. For example, a specific gene or gene fragment, a block of genes, or chromosomes may be affected. Mutation is a genetic change, and the agent that causes the change is called a mutagen.

Genotoxicity is often considered to be similar to mutagenicity; however, genotoxic consequences aren’t usually linked to mutations.

Germ cells and somatic cells can both be affected by mutations. The impact is heritable if the mutation arises in a germ cell. The exposed person has no effect; instead, the effect is handed down to future generations. If the mutation occurs in a somatic cell, the exposed person may experience abnormal cell growth, for example, cancer or cell death-like teratogenesis.

What Are The Relation And Differences Between Carcinogenicity And Mutagenicity?

Mutagens and carcinogens are two physical, chemical, or biological agents that can disrupt an organism’s normal cell division. Mutagens account for approximately 90% of carcinogens. Somatic cell mutations can cause cancers. The main distinction between mutagen & carcinogen is that the former creates a heritable mutation in an organism’s genetic code, whilst the latter causes or encourages cancer in humans and animals. Mutagenesis is the process by which genetic material changes, whereas carcinogenesis is the process by which mutagenic events result in the formation of tumours.

Both mutagens and carcinogens, on the other hand, produce changes in cell division and function. Physical, biological or chemical factors can operate as mutagens and carcinogens. 

Mutagens and carcinogens are two substances that alter the normal functioning and division of cells. Mutagens create alterations in an organism’s genetic information. These alterations have the potential to cause cancer. Carcinogens cause cancer by causing tumours to develop. Physical, chemical, or genetic factors can operate as mutagens and carcinogens. The impact of each agent on microorganisms is the key distinction between mutagen and carcinogen.

Using 532 chemicals assessed in Volumes 1-25 of an IARC Monographs just on Assessment of the Carcinogenic Risks of Chemicals for Humans, the qualitative link between carcinogenicity with mutagenicity (DNA-damaging activity) is studied. About 40 substances (industrial processes) have been proven to be carcinogenic to humans, with 130 chemicals being adequately evaluated in rats and most of them in different short experiments.

Conclusion

The test material is given to the animals daily for a portion of their lives (for example, eighteen months for mice and twenty-four months for rats), preferably via the exposure routes recommended for clinical use. A minimum of three dosing groups with at least fifty animals per group should be included in the study. To unify the selection of dosage regimens for carcinogenicity studies, specific ICH guidelines were produced (ICH 2008a), consisting of various methodologies for determining doses, ranging from toxic metabolites, pharmacokinetics, or pharmacological endpoints to a limited dose.