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Sensitive MALDI-TOF MS and 'turn-on' fluorescent genosensor for the determination of DNA damage induced by CNS acting
Amira F El-Yazbi1, Feda A H Elgammal2, Marwa S Moneeb2
1Department of Chemistry, University of Alberta, Edmonton, AB T6G 2G2, Canada; Faculty of Pharmacy, Department of Pharmaceutical Analytical Chemistry, University of Alexandria, El-Messalah, Alexandria 21521, Egypt.
Abstract:
The genotoxic and carcinogenic adverse effects of various drugs should be considered for assessing drug benefit/risk ratio. On that account, the scope of this study is to examine the kinetics of DNA damage triggered by three CNS acting drugs; carbamazepine, quetiapine and desvenlafaxine. Two precise, simple and green approaches were proposed for probing drug induced DNA impairment; MALDI-TOF MS and terbium (Tb3+) fluorescent genosensor. The results revealed that all the studied drugs induced DNA damage manifested by the MALDI-TOF MS analysis as a significant disappearance of the DNA molecular ion peak with the appearance of other peaks at smaller m/z indicating the formation of DNA strand breaks. Moreover, significant enhancement of Tb3+ fluorescence occurred, proportional to the amount of DNA damage, upon incubation of each drug with dsDNA. Furthermore, the DNA damage mechanism is examined. The proposed Tb3+ fluorescent genosensor showed superior selectivity and sensitivity and is significantly simpler and less expensive than other methods reported for the detection of DNA damage. Moreover, the DNA damaging potency of these drugs was studied using calf thymus DNA in order to clarify the potential safety hazards associated with the studied drugs on natural DNA.
Insights
This study investigated DNA damage from carbamazepine, quetiapine, and desvenlafaxine using MALDI-TOF MS and a terbium fluorescent genosensor. Both methods detected drug-induced DNA strand breaks, highlighting potential safety hazards.
Area of Science:
- Pharmacology
- Toxicology
- Biochemistry
Background:
- Assessing the drug benefit/risk ratio requires understanding genotoxic and carcinogenic effects.
- Central nervous system (CNS) acting drugs like carbamazepine, quetiapine, and desvenlafaxine warrant investigation for potential DNA damage.
Purpose of the Study:
- To examine the kinetics of DNA damage induced by carbamazepine, quetiapine, and desvenlafaxine.
- To evaluate the efficacy of MALDI-TOF MS and a terbium (Tb3+) fluorescent genosensor for detecting drug-induced DNA impairment.
- To clarify the potential safety hazards of these CNS drugs on natural DNA.
Main Methods:
- Matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) was used to detect DNA strand breaks.
- A terbium (Tb3+) fluorescent genosensor was developed and employed to quantify DNA damage.
- Calf thymus DNA was utilized to assess the genotoxic potency of the studied drugs.
Main Results:
- MALDI-TOF MS analysis revealed significant DNA strand breaks induced by all three drugs, indicated by the disappearance of DNA molecular ion peaks.
- Tb3+ fluorescence significantly enhanced upon incubation with the drugs, correlating with the extent of DNA damage.
- The terbium fluorescent genosensor demonstrated superior selectivity and sensitivity compared to existing DNA damage detection methods.
Conclusions:
- Carbamazepine, quetiapine, and desvenlafaxine induce DNA damage, necessitating careful consideration of their safety profiles.
- The developed Tb3+ fluorescent genosensor offers a simple, sensitive, and cost-effective approach for detecting drug-induced DNA damage.
- Further research is warranted to fully elucidate the genotoxic mechanisms and long-term safety implications of these CNS drugs.
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