ABSTRACT

Cell proliferation is regulated by the cell cycle which is controlled by a number of cyclin- dependent kinases (CDKs). The functions of CDKs are critical for cell cycle and are required to traverse checkpoints. A network of inhibitors (CKI) of the cyclin-dependent kinases provide  the important function of regulating the activity of the cyclin complexes. Deregulation ofthese results in either uncontrolled proliferation or cell death (apoptosis). Cell proliferation is an important factor in the development of carcinogenesis induced by genotoxic as well as nongenotoxic carcinogens. It is an integral part of the process of converting DNA adducts to mutations, it also decreases the time that is available for DNA repair and is required to clonal expansion of initiated cell populations. Moreover, cell proliferation increases the number of initiated cells by blocking cell death (apoptosis) and pertubing checkpoins in the cell cycle. Two major mechanisms of induction of cell proliferation (regenerative and mitogens-stimulated) were discussed in relation to their potential roles in the carcinogenicity.