Cell Cycle Response to Isocyanates and Onset of Cyclin E Expression in Cultured Mammalian Cells

Cell cycle comprises the vital mechanism exposed to environmental toxic chemicals resulting in imbalance of cell cycle and finally ends with cancer. Cancer is a multistage process, which involves a series of genetic alterations that begins with genomic instability provoked by certain factors such as DNA damage, deregulation of CDKs, cyclins and end with the development of cancer. Key transitions in the cell cycle are regulated by the activities of various protein kinase complexes composed of cyclin and cyclin-dependent kinase (Cdk) molecules. An isocyanate is one of the highly reactive industrial intermediates, possesses the capability to modulate the bio-molecules by forming toxic metabolites and adducts which may cause adverse health effects. We find out the molecular mechanism of methyl isocyanate genotoxicity on cell cycle regulatory protein and also evaluate the expression of cyclin E protein in cultured mammalian cell lines (MM55.K & NIH/3T3) after exposure to isocyanate (Nsucinamidyl N-methylcarbamate). Extended exposure to isocyanates causes overexpression of Cyclin E and CDK2 and ultimately leads to genetic alteration in NIH/3T3 cells. This information could be useful to design of new approaches for risk assessment of potential industrial disasters.