Two experts in Toxicology from Laboratorios Esteve, Antonio Guzmán Cano and Antonio Rodríguez Fernández de Henestrosa, gave one of the conferences of the Meetings of the Master's Degree in research, development and Innovation of Medicines (MIDI) of the School of Pharmacy and Nutrition of the University of Navarra, whose goal consists of putting on contact the student with the latest trends and relevant topics of the sector. On this occasion, the two experts explained how programs of study genotoxicity tests are carried out, which are essential in the development of any drug to avoid inducing alterations in the genetic material.

- First of all, what is genotoxicity?
The term "genotoxicity" refers reference letter to the induction of alterations in the genetic material. These alterations can occur spontaneously due to endogenous causes (errors in replication), or as a consequence of exhibition to physical (radiation), chemical (chemicals) or biological (oncoviruses) agents. In this sense, the genotoxicity programs of study evaluates the capacity of these environmental agents (including drugs) to cause damage to genetic material. When this damage is fixed and transmitted to the cellular progeny, what we call a mutation occurs: a heritable change in the genetic material.

- Why is it important to assess genotoxicity?
Genotoxic damage is considered to be involved in the production of a wide range of pathological conditions. Among them, its role in carcinogenic processes is particularly relevant, where the induction of mutations would be a necessary initiating event for neoplastic processes (abnormal cell growth).

Likewise, the induction of genetic damage on germline cells may carry an associated risk of transmitting mutations to offspring that confer adverse phenotypic properties.

- How important is the assessment of genotoxicity in the development of drugs?
Given the importance of adverse effects associated with genotoxic activity, a drug that exhibits genotoxic properties will rarely be C for commercial use. Consequently, drugs with genotoxic properties are usually discarded during the process of development. Only under very specific conditions, such as a life-threatening disease, can the risk-benefit balance be favorable to the use of a genotoxic drug.

- How do pharmaceutical companies study it during the development of a drug?
During the development phase, the genotoxic potential of a drug is evaluated by means of a battery of three complementary genotoxicity regulatory assays, as established by directive ICH S2 (R1). The performance of this battery involves the use of experimental models in vitro (bacteria and mammalian cells) and in vivo (generally rodents), which evaluate the ability of the drug under study to produce genotoxic effects on the different structural levels of the genetic material (gene, chromosome and chromosomal endowment).

It is important to add that, before reaching the development phase, screening tests (non-regulatory) are frequently used to identify and rule out compounds with genotoxic potential, thus minimizing the likelihood that they will be considered candidates for development.