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Published on: January 10, 2015
Tobacco Smoke Carcinogens Induce DNA Repair Machinery Function Loss: Protection by Carbon Nanotubes
Anukriti Dhasmana1, Anupam Dhasmana1,2, Hobani Yahya H3
1Himalayan School of Biosciences, Swami Rama Himalayan University, Dehradun (Uttarakhand), India.
Purpose:
DNA damage is a continuous process occurring within the cells caused by intrinsic and extrinsic factors, but it gets repaired regularly. If the DNA repair process is faulty, the incidences of damages/mutations can accumulate in cells resulting in cell transformation. It is hypothesized that the negative variations in DNA repair pathways in even at one point viz. genetic, translational or posttranslational stage may fairly be crucial for the beginning and development of carcinogenesis. Therefore, we investigated the potential of tobacco specific nitrosamines (TSNs) related carcinogens to interact with the enzymes involved in DNA repair mechanisms in the current study.
Methods:
The derivatives of cigarettes' smoke like NNK and NNAL are very well known and recognized carcinogens. Therefore, almost 120 enzymes playing crucial role in the DNA repair process have been analysed for their reactivity with NNK and NNAL.
Results:
The molecular docking study helped to screen out, 07 possible DNA repair enzyme targets for NNK, and 12for NNAL. Present study revealed the loss of activity of DNA repair enzymes in the presence of NNK and NNAL, and this accumulation may induce the tendency of DNA damage which can lead the transformation of exposed normal cells in to cancerous cells. This study also demonstrated the protective potential of nanoparticles like SWCNTs/MWCNTs against TSN's induced toxicity; here SWCNT against NNK (-17.16 Kcal/Mol) and MWCNT against NNK -17.01 Kcal/Mol were showing maximum binding affinities than the known biomolecular target of NNK 1UGH (Uracil-DNA glycosylase,-7.82Kcal/Mol).
Conclusion:
CNTs can be applied as chemo-preventive agents against environmental and tobacco induced carcinogens owing to their scavenging potential and warrants for in vivo and in vitro experimental validation of the results obtained from the present study.
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Insights
Tobacco-specific nitrosamines (TSNs) like NNK and NNAL can impair DNA repair enzymes, potentially leading to cancer. Carbon nanotubes (CNTs) show promise as protective agents against TSN-induced DNA damage.
Area of Science:
- Biochemistry
- Molecular Biology
- Nanotechnology
Background:
- DNA damage is a continuous cellular process.
- Faulty DNA repair can lead to mutations and cell transformation, initiating carcinogenesis.
- Tobacco-specific nitrosamines (TSNs) are known carcinogens implicated in various cancers.
Purpose of the Study:
- To investigate the interaction between TSN carcinogens (NNK and NNAL) and DNA repair enzymes.
- To explore the potential of carbon nanotubes (CNTs) as protective agents against TSN-induced toxicity.
Main Methods:
- Molecular docking studies were employed to analyze the reactivity of approximately 120 DNA repair enzymes with NNK and NNAL.
- Binding affinities of CNTs (SWCNTs/MWCNTs) with NNK were calculated and compared to known enzyme-carcinogen interactions.
Main Results:
- NNK and NNAL were identified as potential inhibitors of 7 and 12 DNA repair enzymes, respectively.
- The study demonstrated that SWCNTs and MWCNTs exhibit significant binding affinities to NNK, suggesting a protective effect.
- CNTs showed higher binding affinities compared to the known biomolecular target of NNK, Uracil-DNA glycosylase (1UGH).
Conclusions:
- CNTs possess chemo-preventive potential against environmental and tobacco-induced carcinogens due to their scavenging capabilities.
- The findings suggest that CNTs could be developed as therapeutic agents for TSN-induced cancers.
- Further in vivo and in vitro experimental validation is warranted to confirm these results.
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