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.

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.

Lead Exposure in Different Organs of Mammals and Prevention by Curcumin-Nanocurcumin: a Review.

Chronic lead exposure is related to many health diseases in mammals. Exposure to lead forms reactive oxygen species reducing body antioxidant enzymes inflicting injury to numerous macromolecules or cell necrosis. Recent studies have revealed oxidative stress as the vital mechanism for lead toxicity. Lead is found to be toxic to several organ systems such as hematopoietic, skeletal, renal, cardiac, hepatic, and reproductive systems and extremely toxic to the central nervous system (CNS). Curcumin, an active ingredient of the dietary spice, and nanocurcumin, a nanoform of curcumin, are found to decrease toxicity due to lead in various organ systems in mouse models. Higher bioavailability, chelating property, and retention time of nanocurcumin over bulk curcumin may pave the way to expand the utility of nanocurcumin to remove lead toxicity from various organ systems within humans.