Biochemical studies on the effect of stress on DMBA -TPA induced carcinogenesis

Abstract

Cancer is one of the leading causes of death in most well developed countries. It has been established that multiple stepwise alterations of the original genome information are major molecular mechanisms responsible for carcinogenesis. It is postulated that cancer is one of those diseases in which reactive oxygen species (ROS) and reactive nitrogen species (RNS) are involved in its pathogenesis, but the exposure to a number of psychological factors may intensify the process of free radical generation thereby enhancing the incidence of cancer. Psychological stress, a common phenomenon, generally a state of disturbed homeostasis, harmony and equilibrium is attracting increasing attention due to its implication in wide range of diseases including cancer. Various mechanisms have been considered as possible mediators of the effect of stress on neoplastic process, which include alterations in the immune and/or neuroendocrine system and in the antioxidant defense status. Altered antioxidant status indicates production of reactive oxygen species such as peroxides, hydroxyl and superoxide anion radicals. There is accumulating evidence to indicate that stress can stimulate numerous pathways leading to an increased production of free radicals. In situations of oxidative stress, reactive oxygen and nitrogen species causes DNA single- and double-strand breaks, crosslinks and a variety of other modifications, leading to altered genome information in spite of the robust counter measures enacted by repair enzymes and apoptotic pathways. Oxidative stress induces a cellular redox imbalance which has been found to be present in various cancer cells compared with normal cells; the redox imbalance thus may be related to oncogenic stimulation. Environmental toxicants play key roles in cell transformation and tumorigenesis and their study is a high priority to defining risk factors associated with human exposure.