Journal of Clinical Pharmacology and Toxicology is using Editorial Tracking System to maintain quality and transparency to the author in the peer-review process. Review processing will be performed by the editorial board members of the Journal of Clinical Pharmacology and Toxicology or by Reviewers (outside experts in the field). Two independent reviewer’s approval (Minimum reviewer’s approval) followed by editor approval is obligatory for acceptance of any manuscript excluding an editorial.

Introduction

In genetics, genotoxicity describes the property of chemical agents that damages the genetic information within a cell causing mutations, which may lead to cancer. While genotoxicity is often confused with mutagenicity, all mutagens are genotoxic, whereas not all genotoxic substances are mutagenic. The alteration can have direct or indirect effects on the DNA: the induction of mutations, mistimed event activation, and direct DNA damage leading to mutations. The permanent, heritable changes can affect either somatic cells of the organism or germ cells to be passed on to future generations. Cells prevent expression of the genotoxic mutation by either DNA repair or apoptosis; however, the damage may not always be fixed leading to mutagenesis.

Assay

To assay for genotoxic molecules, researchers assay for DNA damage in cells exposed to the toxic substrates. This DNA damage can be in the form of single- and double-strand breaks, loss of excision repair, cross-linking, alkali-labile sites, point mutations, and structural and numerical chromosomal aberrations. The compromised integrity of the genetic material has been known to cause cancer. As a consequence, many sophisticated techniques including Ames Assay, in vitro and in vivo Toxicology Tests, and Comet Assay have been developed to assess the chemicals' potential to cause DNA damage that may lead to cancer.

As a part of safety evaluation process, regulatory authorities all over the globe require information on the genotoxic potential of the new drugs. Genotoxicity is usually evaluated along with other toxicological end points during the safety assessment.

Testing

During the early testing stages; the same testing assays are carried out for predicting both the potential heritable germ cell damage as well as the carcinogenicity because these endpoints have common precursors. The relationship between exposure to particular chemical and carcinogenesis has been established whereas such relationship has been difficult to establish for heritable diseases, genotoxic studies have been mainly associated and used for the prediction of carcinogenicity of a compound.

The damage to the genetic material is caused by the interactions of the genotoxic substance with the DNA structure and sequence. These genotoxic substances interact at a specific location or base sequence of the DNA structure causing lesions, breakage, fusion, deletion, mis-segregation or nondisjunction leading to damage and mutation.

Reactive oxygen species are known to be genotoxic in nature, thus any chemical or substance that may increase the reactive oxygen species (ROS) production might evidently add to the endogenously produced ROS and may lead to non-linear relationships of dose-effect.  The agents that are capable of damaging the DNA directly or indirectly are electrophilic species that form covalent adducts to the DNA, reactive oxygen species, ultra violet and ionizing radiations, nucleoside analogues, topoisomerase inhibitors and protein synthesis inhibitors. For example, in its high-valent oxidation state the transition metal chromium interacts with the DNA so that DNA lesions occur, leading to carcinogenesis.

Regards

Mary Wilson

Editorial office

Journal of Clinical Pharmacology and Toxicology

E-mail: pharmatoxicol@eclinicalsci.com