Glutathione Conjugation and DNA Adduct Formation of Dibenzo[a,l]pyrene and Benzo[a]pyrene Diol Epoxides in V79 Cells Stably Expressing Different Human Glutathione Transferases

2002 ◽  
Vol 15 (2) ◽  
pp. 170-179 ◽  
Author(s):  
Kathrin Sundberg ◽  
Kristian Dreij ◽  
Albrecht Seidel ◽  
Bengt Jernström
Keyword(s):  
Adduct Formation ◽  
Dna Adduct ◽  
Glutathione Transferases ◽  
V79 Cells ◽  
Glutathione Conjugation ◽  
Diol Epoxides

scholarly journals Computational Exploration of Dibenzo [a,l] Pyrene Interaction to DNA and its Bases: Possible Implications to Human Health

2020 ◽  
Vol 11 (4) ◽  
pp. 11272-11283
Keyword(s):  
Weak Interactions ◽  
Excision Repair ◽  
Computational Simulation ◽  
Environmental Pollutant ◽  
Adduct Formation ◽  
Dna Adduct ◽  
Enzymatic Reactions ◽  
Diol Epoxides ◽  
Computational Exploration ◽  
Cis And Trans

Dibenzo[a,l]pyrene (DBP), an environmental pollutant, undergoes a series of enzymatic reactions yielding electrophilic diastereomeric diol-epoxides (DEs) that subsequently bind to DNA covalently and hampers the healing mechanism of cascaded biological pathways resulting in onset of different diseases. In the proposed work, we meticulously investigated and elucidated the mechanistic details of DNA adduct formation and nucleotide excision repair (NER) pathway proteins interaction with all possible diastereomers of dibenzo[a,l]pyrene-diol-epoxides (DBPDEs) namely- (±)-anti-, (±)-syn-, trans- and cis- forms of (-)-anti- and (+)-syn- DBPDEs through a computational simulation study. Our findings revealed that (±)-anti- and (-)-syn-DBPDEs interact more strongly with dT20 while (+)-syn-DBPDE exhibits strong interaction with dG6. Moreover, cis- and trans-conformations of (-)-anti- and (+)-syn-DBPDEs depicted strong binding towards N6-dA. Furthermore, aforesaid metabolic intermediates exhibited weak interactions with NER proteins. This imbalance of interaction tendencies relatively favors the DNA-adduct formation than the NER pathway. Based on our computational data, a robust understanding of the underlying molecular mechanism(s) of DBP-DNA interactions may subsequently lead to the design of novel potential compounds to exert inhibition and block its DNA binding ability and eventually facilitate cancer prevention.

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