Adverse Effects Caused by Adaptive Imbalance to Genotoxic Stress after Infection and Inflammation

Abstract

Abstract

Cancer is a consequence of genomic damage and mutation, which can arise from various causative agents including infection, inflammation and exposure to genotoxic agents, i.e. ultraviolet light, carcinogens.  To protect the genome against the abnormality or mutation, cells have evolved genotoxic stress responses to activate an appropriate repair pathway, or, in the case of irreparable, apoptosis would be induced. The defense mechanism consists of a set of different pathways that are xenobiotic mechanism, antioxidant process, cell cycle arrest, DNA repair system, and apoptosis. Nevertheless, numbers of evidence show that these responses may have adverse effects arising from the imbalanced action of the above-mentioned pathways which, in turn, may accelerate cancer development. It has been hypothesized that if the stress is not consistent with intermittent lapses in genotoxic stress, there will be the down-regulation of these adaptive proteins and enzymes, possibly leading to a greater amount of cellular damage than with chronic exposure. This hypothesis is supported by the epidemiological finding of significantly increased risk of skin cancer with multiple sunburns. Another supported data is the cigarette smoke in experimental animals causing an adaptive increase in gene expression patterns which return to normal when the exposure is interrupted.  These findings suggested that the imbalance of adaptive responses to genotoxic stress can drive cells to enter pro-carcinogenic stage.

 Key words: infection, inflammation, genotoxic stress, adaptive imbalance, pro-carcinogenic consequences