Genotoxicity: Damage to DNA and Its Consequences.

Many chemical agents have a property of causing damage to the DNA which may lead to cancer are called as genotoxins and this property of such chemical agents is called as genotoxicity. Genotoxicity is generally confused with mutagenicity but they show a few differences in them. All mutagens are genotoxic while all genotoxins are not mutagens. These DNA alterations cause can have both direct as well as indirect effects on the DNA. The direct DNA damage leads to mutations. These changes can affect both somatic as well as germ cells. So, changes on germ cells are inheritable to the next generations. Every cell has a tendency to prevent the expression of these genotoxic mutations either by DNA repair or apoptosis. When this repairing mechanism fails then it leads to mutagenesis.The DNA damage so happened can be in the form of single strands or double strand breaks, point mutations, loss of repair, cross linking and chromosomal aberrations. The compromised integrity of genetic material leads to cause cancer.

Cancer is one of the leading causes of deaths worldwide. The agents capable of causing damage to genetic material are known as genotoxins and, according to their mode of action, are classified into mutagens, carcinogens or teratogens. Genotoxins are involved in the pathogenesis of several chronic degenerative diseases including hepatic, neurodegenerative and cardiovascular disorders, diabetes, arthritis, cancer, chronic inflammation and ageing. In recent decades, researchers have found novel bioactive phytocompounds able to counteract the effects of physical and chemical mutagens. Several studies have shown potential antigenotoxicity in a variety of fruits. Grapefruit, cranberries, pomegranate, guava, pineapple, and mango which are frequently consumed by humans, as well as the analysis of some phytochemicals extracted from fruits and yeasts which have demonstrated antigenotoxic capacity in various tests, including the Ames assay, sister chromatid exchange, chromosomal aberrations, micronucleus and comet assay.

Genotoxicity is the ability of different agents to produce damage to genetic material. However, the damage induced in the genetic material includes not only DNA, but also all those cellular components related to the functionality and behavior of chromosomes within the cell. An example of this are the proteins involved in the repair, condensation and decondensation of DNA in the chromosomes, or other structures as the mitotic spindle, responsible for distribution of the chromosomes during cell division. The agents capable of causing genetic toxicity are described as genotoxic or called genotoxins; and according to their origin, they are classified into three categories: physical, chemical and biological. The first category includes the ionizing and electromagnetic radiation, temperature and ultraviolet light. The second group consists of a wide range of compounds with multiple effects, highlighting the heavy metals, pesticides, aromatic hydrocarbons, alkylating agents, acridine, acrylamide, aliphatic epoxides, organic solvents, asbestos particles, food additives and xenobiotics resulting from certain “lifestyles” such as smoking or drinking (alcoholism). The last category considers some parasites, bacteria, plants, viruses and fungi (specifically those that synthesize secondary metabolites such as mycotoxins).

At the same time, genotoxic agents may also be classified according to their effects or mode of action into mutagens, carcinogens or teratogens, resulting in three types of processes: mutagenesis, carcinogenesis and teratogenicity. Mutagenesis considers, basically, two types of genetic alterations. Alterations (mutations) that may occur at the level of a minimum unit of information (gene) or higher-level units, such as structural groups (chromosomes), to what is called micro mutation or macromutation, respectively. In the case of macromutations, the clastogenic agents are defined as those capable of inducing chromosome breaks and the aneunogen agents, those who produce the loss of whole chromosomes or chromosome sets. Mutations may occur on somatic and/or germ cells, being in the latter case inheritable if they are transmitted to the progeny. There is increasing evidence that mutations in somatic cells are not only involved in the carcinogenesis but can also cause genetic disorders such as arteriosclerosis, heart diseases and several other chronic degenerative diseases.