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Chemistry Behind Genotoxicity and Mutagenicity

Table of Contents

• Introduction and Outcome
• Genotoxic chemicals
• Chemistry behind Genotoxicity
• Structure Alerts (SAs) concept
• Genotoxicity and Mutagenicity
  • Difference between Genotoxicity and Mutagenicity
• Conclusion
• FAQs

Introduction and Outcome

The Genotoxic and Mutagenic chemicals can damage the DNA and that is why these chemicals can be carcinogenic. The meaning of Genotoxicity is to damage the DNA or genetic material. The DNA can be damaged by various sources and one of them is genotoxic chemicals or mutagenic chemicals. In this article, I will share my skill-based knowledge on chemistry behind genotoxicity and mutagenicity and structure alert concept. After reading the post, all your doubts related to genotoxicity and mutagenicity will be cleared.

Genotoxic chemicals

DNA can be damaged by various sources and one of them is Genotoxic chemicals. These chemicals can cause genetic mutations, chromosomal breakage, chromosomal rearrangements, cancer and other adverse effects at very low levels. hence, genotoxicity can be defined as ” Genotoxicity is the ability of any chemical to damage DNA”

Chemistry behind Genotoxicity

To understand genotoxicity, we must first understand the structure of DNA, its components and the possible way by which DNA can be damaged.

To understand Genotoxicity, we must first understand the structure of DNA, its components and the possible ways in which DNA can be damaged. The following are the possible path in which DNA can be damaged:

• Cross linking
• Oxidative
• Adduct formation and
• Strand breaks

DNA is a double helix formed by base pairs attached to a sugar-phosphate backbone. The following are the base pairs:

• Adenine (A) – Thiamine (T)
• Guanine (G) – Cytosine (C)

Hence, any chemicals or agent which can alter the identity of these bases can damage the DNA. Now the question is how the identity of these bases can be affected

Hence, any chemical/agent which can alter the identity of these bases can damage DNA. Now the question is how the identity of these bases can be affected. To understand the same let us discuss the structure of these bases. The following are the structures of these base pairs:

From the above structures, it is clear that these bases of DNA have multiple Nitrogen atoms. Since each Nitrogen atom contains one lone pair of electrons and hence these bases are electron rich compounds and hence can donate or share electrons with other chemicals in bond formation. It mean these bases act as nucleophiles’

Now the question is which type of chemicals can interact with the above base?

Electron-deficient molecules/cations / carbonium ions can accept the electron and make the bond with these bases. It means an Electrophile may attack on these bases and can affect the identity of DNA. Hence, Genotoxins can be defined as:

“Genotoxins are either electrophiles’ per se or can be activated to electrophilic reactive intermediates in vivo”

Structure Alerts Concept of SAs concept

Electrophiles or Electrophilic reactive intermediates can combine with nucleophilic part of DNA (base-pairs of DNA) and can damage the DNA. Substructure or functional groups of above characteristics are genotoxic in nature and call Structure Alerts concept or SAs concept. SAs concept is one of the most useful scheme to assess carcinogenic potential of an untested molecule and it is very helpful in pharmaceuticals development.

Genotoxicity and Mutagenicity

Mutagenicity refers to the induction of permanent transmissible changes in the amount or structure of the genetic material of cells or organisms/DNA. It is associated with Mutation.The chemical/ agent causing the change is called Mutagen.

Genotoxicity is similar to Mutagenicity except the genotoxic effects are not necessary associated with mutations.

Difference between Genotoxicity and Mutagenicity

• All Mutagens are genotoxic, however, not all Genotoxins are mutagenic
• The mutagenicity effect is passed on to future generations whereas Genotoxicity is not

Conclusion

Controlling Genotoxins/Mutagens is the challenging task for a pharmaceutical profesional. It needs both knowledge and integrated skills. I hope this post has enhanced your knowledge to the next level and now you can effectively control Genotoxins and Mutagens in pharmaceuticals. Write your learning/suggestions in the comment section.

FAQs

What is Genotoxicity and Mutagenicity?

The ability of a chemical to damage DNA is called Genotoxicity or Mutagenicity

What is the chemistry behind Genotoxicity?

All Genotoxic chemicals are electrophiles.

What is difference between Genotoxicity and Mutagenicity

All Mutagens are genotoxic, however, not all Genotoxins are mutagenic.The mutagenicity effect is passed on to future generations whereas Genotoxicity is not

Abbreviations:

• DNA: Deoxyribonucleic acid
• SAS: Structure Alerts

References:

• Genotoxic impurities; Strategies for identification and control-Andrew Teasdale
• https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/mutagenicity