title: In silico docking of methyl isocyanate (MIC) and its hydrolytic product (1, 3-dimethylurea) shows significant interaction with DNA Methyltransferase 1 suggests cancer risk in Bhopal-Gas- Tragedy survivors.
abstract: DNA methyltransferase 1 (DNMT1) is a relatively large protein family responsible for maintenance of normal methylation, cell growth and survival in mammals. Toxic industrial chemical exposure associated methylation misregulation has been shown to have epigenetic influence. Such misregulation could effectively contribute to cancer development and progression. Methyl isocyanate (MIC) is a noxious industrial chemical used extensively in the production of carbamate pesticides. We here applied an in silico molecular docking approach to study the interaction of MIC with diverse domains of DNMT1, to predict cancer risk in the Bhopal population exposed to MIC during 1984. For the first time, we investigated the interaction of MIC and its hydrolytic product (1,3-dimethylurea) with DNMT1 interacting (such as DMAP1, RFTS, and CXXC) and catalytic (SAM, SAH, and Sinefungin) domains using computer simulations. The results of the present study showed a potential interaction of MIC and 1,3-dimethylurea with these domains. Obviously, strong binding of MIC with DNMT1 interrupting normal methylation will lead to epigenetic alterations in the exposed humans. We suggest therefore that the MIC- exposed individuals surviving after 1984 disaster have excess risk of cancer, which can be attributed to alterations in their epigenome. Our findings will help in better understanding the underlying epigenetic mechanisms in humans exposed to MIC.
authors.affiliation: School of Biotechnology, Rajiv Gandhi Technological University, Bhopal, India E-mail : Inbesat.Epig@gmail.com.
authors.forename: Inbesat
authors.initials: I
authors.lastname: Khan
authors.forename: Chinnu Sugavanam
authors.initials: CS
authors.lastname: Senthilkumar
authors.forename: Nisha
authors.initials: N
authors.lastname: Upadhyay
authors.forename: Hemant
authors.initials: H
authors.lastname: Singh
authors.forename: Meenu
authors.initials: M
authors.lastname: Sachdeva
authors.forename: Suresh Kumar
authors.initials: SK
authors.lastname: Jatawa
authors.forename: Archana
authors.initials: A
authors.lastname: Tiwari
mesh_terms: D001665:Binding Sites; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000378:metabolism*; D019175:DNA Methylation / Q000187:drug effects*; D004781:Environmental Exposure / Q000009:adverse effects*; D006801:Humans; D007194:India / Q000453:epidemiology; D017953:Isocyanates / Q000378:metabolism* / Q000633:toxicity; D008782:Methylurea Compounds / Q000378:metabolism*; D062105:Molecular Docking Simulation; D009369:Neoplasms / Q000139:chemically induced* / Q000453:epidemiology; D011485:Protein Binding; D017434:Protein Structure, Tertiary
chemical_list: D017953:Isocyanates; D008782:Methylurea Compounds; C008461:methyl isocyanate; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; C000619380:DNMT1 protein, human; C018276:1,3-dimethylurea