GENOTOXICITY

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ABOUT AUTHORS
L Reddenna1*, Dr. P. Venkatesh1, K Siva Kumar2, A Sai keshava Reddy2
1* Department of Pharmacy Practice,
Jagan’s College of Pharmacy,
Nellore, Andhra Pradesh, India
2 Department of Pharmacy Practice,
Nirmala College of Pharmacy,
Kadapa, Andhra Pradesh, India
*reddennapharmd@gmail.com

ABSTRACT
Genotoxicity describes the possessions of chemical agents that damage the genetic information within a cell causing mutations, which may lead to cancer. Heritable changes can influence either somatic cells of the organism or germ cells to be passed on to future generations. As a result, many urbane techniques including Ames Assay, in vitro and in vivo Toxicology Tests, and Comet Assay have been developed to evaluate the chemicals probable to cause DNA damage that may lead to cancer. The genotoxic substances provoke damage to the genetic material in the cells through exchanges with the DNA sequence and structure. Genotoxicity testing is to resolve if a substrate will sway genetic material or may cause cancer. Genotoxic Chemotherapy is the treatment of cancer with the use of one or more genotoxic drugs. The treatment is traditionally part of standardized regime. By utilizing the destructive properties of genotoxins treatments aims to induce DNA damage into cancer cells.

REFERENCE ID: PHARMATUTOR-ART-2523

PharmaTutor (Print-ISSN: 2394 - 6679; e-ISSN: 2347 - 7881)

Volume 5, Issue 9

Received On: 13/04/2017; Accepted On: 22/05/2017; Published On: 01/09/2017

How to cite this article: Reddenna L, Venkatesh P, Kumar KS, Reddy ASK;Genotoxicity; PharmaTutor; 2017; 5(9);23-34

INTRODUCTION
Genotoxicity describes the possessions of chemical agents that damage the genetic information within a cell causing mutations, which may lead to cancer. Genotoxicity is perplexed with mutagenicity; all mutagens are genotoxic, while not all genotoxic substances are mutagenic. The variation can have direct or indirect effects on the DNA
•  The induction of mutations
•  Mistimed event activation
•  Direct DNA damage leading to mutations.

Genetic Toxicology
• Study of an agent’s ability to induce genetic damage
• Subspecialty of toxicology
• Current paradigm developed over last 30 years
• Short-term in vitroand in vivogenetic toxicology tests [1]

Figure-1: It displays the genotoxic risk

Heritable changes can influence either somatic cells of the organism or germ cells to be passed on to future generations. Cells avert expression of the genotoxic mutation by either DNA repair or apoptosis; Conversely, the smash up may not always be preset leading to mutagenesis. To assay for genotoxic molecules, DNA damage in cells exposed to the toxic substrates. This DNA damage can be in the type of single and double strand breaks, thrashing of excision repair, cross-linking, alkali labile sites, point mutations, and structural and numerical chromosomal aberrations. The compromised veracity of the genetic material has been known to cause cancer. As a result, many urbane techniques including Ames Assay, in vitro and in vivo Toxicology Tests, and Comet Assay have been developed to evaluate the chemicals probable to cause DNA damage that may lead to cancer.

Figure-2: Single and double strand DNA damage potentially caused by genotoxins

Mechanisms
The genotoxic substances provoke damage to the genetic material in the cells through exchanges with the DNA sequence and structure. Example, the transition metal chromium interacts with DNA in its high valent oxidation state so to incur DNA lesions leading to carcinogenesis. A research performed to study the interface between DNA with the carcinogenic chromium by using a Cr (V) Salen complex at the specific oxidation state. The interface was explicit to the guanine nucleotide in the genetic sequence. High-valent chromium is seen to act as a carcinogen; found that the mechanism of damage and base oxidation products for the interaction between high-valent chromium and DNA are applicable to in vivo formation of DNA damage leading to cancer.

Figure-2: Transitions and transversions

An additional example of a genotoxic substance causing DNA damage is pyrrolizidine alkaloids (PAs). These substances are found mostly in plant species and are poisonous to animals, including humans; About half of them have been acknowledged as genotoxic and many as tumorigenic. The pyrrolizidine alkaloids are mutagenic in vivo and in vitro and, therefore, accountable for the carcinogenesis outstandingly in the liver. [2]

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