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Published on: November 12, 2017
4-Chloro-orthophenylenediamine alters DNA integrity and affects cell survival: inferences from a computational,
Shifa Khan1, Asif Ali1, Moinuddin1
1Department of Biochemistry, Faculty of Medicine, Jawaharlal Nehru Medical College, Aligarh Muslim University, Aligarh, India.
Abstract:
The deleterious impact of toxic constituents of hair dyes over the human health has gained immense attention in the recent past. Their oncogenicity, mutagenicity, role in protein modification, impact on cellular metabolism has been documented. There is little information on the mechanism of reactivity of hair dye components with the nucleic acids and its implications. This work, therefore, uses computational, biophysical/biochemical, microscopic and cell-based study to analyze the interaction of monocyclic aromatic amine and a hair dye component, 4-chloro-orthophenylenediamine (4-Cl-OPD) with the DNA, its impact on DNA structure and cell survival. The results suggest that 4-Cl-OPD binds with the DNA in minor groove of the duplex involving three base pairs preferentially the G-C residues, induces strand breaks and makes DNA thermally labile through loss of hydrogen bonding/base unstacking. 4-Cl-OPD causes fragmentation of DNA, reduction in size of the molecule, alters B-DNA conformation and disrupts its secondary structure. The modified DNA gives fragmented appearance, shows broken strands and aggregation in ultra-structural analysis. 4-Cl-OPD induces ROS generation in lymphocytes, increases the comet's average tail length and reduces the viability of lymphocytes. This study forms a base for establishing the direct toxicity of 4-Cl-OPD at the molecular and cellular level through direct production of superoxide radicalCommunicated by Ramaswamy H. Sarma.
Insights
Hair dye component 4-chloro-orthophenylenediamine (4-Cl-OPD) directly interacts with DNA, causing structural damage and cell death. This study reveals its molecular mechanisms, including DNA binding and oxidative stress induction in lymphocytes.
Area of Science:
- Toxicology
- Molecular Biology
- Biochemistry
Background:
- Hair dyes contain toxic compounds with documented health risks like carcinogenicity.
- Limited understanding exists regarding the interaction mechanisms between hair dye components and nucleic acids.
Purpose of the Study:
- To investigate the molecular interactions of 4-chloro-orthophenylenediamine (4-Cl-OPD), a hair dye component, with DNA.
- To assess the impact of 4-Cl-OPD on DNA structure, integrity, and cellular viability.
Main Methods:
- Computational analysis
- Biophysical and biochemical assays
- Microscopic examination
- Cell-based studies using lymphocytes
Main Results:
- 4-Cl-OPD binds to the minor groove of DNA, preferentially at G-C rich regions, inducing strand breaks and thermal instability.
- Observed DNA fragmentation, reduced molecular size, altered B-DNA conformation, and disrupted secondary structure.
- 4-Cl-OPD triggered reactive oxygen species (ROS) generation, increased DNA tail length in comet assays, and reduced lymphocyte viability.
Conclusions:
- 4-Cl-OPD exhibits direct molecular and cellular toxicity by interacting with DNA and inducing oxidative stress.
- The findings establish a mechanistic link between hair dye components and DNA damage, impacting cell survival.
