A toxic compound can interact with DNA by intercalation or groove binding then leading probably to DNA damage (cleavage).
Does DNA interaction without any damage mean "genotoxicity"?? or DNA must be cleaved and damaged to talk about genotoxicity??
Dear Mohammed, this is interesting question. I will follow what was stated in Wikipedia:
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.
Your definition of genotoxicity is correct, it means damage to DNA produced by a chemical compound or a physical agent.
Mutagenes may be genotoxic. But that does not mean that a mutagen is always genotoxic.
Otherwise the Darwinian evolution would have not existed.
Thanks Mr. Koltai for your explanation.
let's take the case of photosensitizer:
a) concerning photodynamic therapy of cancer (PDT), we have a photosensitizer called TPPS4 that reach the nucleus upon light exposure and bring about DNA photooxidative damage (via ROS generation). Here we can talk about photogenotoxicity.
b) There are many photosensitizers that exert dark toxicity; it could be cytotoxiciy or genotoxicity. In case of genotoxicity, I am wondering if the photosensitizer must damage the DNA to cause that genotoxicity or it can only interact with DNA then leads to genotoxicity? (keep in mind that interaction DNA-photosensitizer without cleavage is well reported in vitro).
Actually a photosensitizer will make DNA more "fragile" to the photonic energy source. We may say that photon plus photosensitizer work in tandem to produce genotoxicity.
Thanks for nice question. I am enjoying the discussion regarding very interesting and important issue of genotoxicity. I must say, I am not expert in this particular field. However, some of my works related to DNA strand breaks/damages. But, my opinion is until what degree of interaction we may called it genotoxicity? As, in general toxicity is somehow out of tolerance limit to make changes in general. So, the interaction might not genotoxic until a definite limit. Thank you. Best wishes
You are welcome Mr. Rahman. Thank you for your meaningful comment.
Until what degree of interaction we may called it genotoxicity? That is what I am looking for..
There is no definition about limits. But I will try to invent one:
A physical or chemical agent is genotoxic when introduces irreversible modifications in coding sectors of DNA with alteration of the protein coded by that gene.
So such modifications in DNA coding sequences can be carried out upon simple interaction (through chemical bonds as hydrogen bonds for example) with a chemical agent. Am I right?
You are right. But usually the interaction creates an irreversible change that cannot be corrected by "genoma gatekeepers".
I would like to mention the interaction of Netropsin which is a fungal toxic substance with DNA. Netropsin binds to the minor groove of DNA via hydrophobic and hydrogen bonds (non-intercalative mechanism) and interfers with replication and transcription causing therefore genotoxicity.
Thanks Mr. Koltai for that discussion.
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