Chapter 6 - Autophagy in arsenic exposed population and cancer patients

Abstract

Arsenic a genotoxic metalloid has become a major threat to the living world in the present scenario. Its distribution in the environment and the many sources of exposure make it more hazardous to humanity. Various sources of arsenic exposure from contaminated groundwater have become a global public health concern, with over 300 million people affected worldwide. Bihar is the second most arsenic-affected state after West Bengal in India. Out of 38 districts of Bihar, 22 districts have been severely affected by arsenic. It is estimated that currently 10 million population are exposed to arsenic in the state. The exposed population is continuously consuming potable water contaminated with arsenic above the WHO recommended concentration of 10μg/L. It is currently associated with several health problems, including skin, liver, lung, kidney, prostate, and gallbladder cancer. Moreover, the exposed population is also exhibiting severe health-related problems such as skin manifestations—hyperkeratosis, melanosis, raindrop pigmentation, loss of appetite, gastrointestinal problems, anemia, hormonal disorders, etc. The International Agency for Research on Cancer has also classified the disease as a Group I human carcinogen. The mechanism of the arsenic-induced tumor involves alteration of DNA repair, methylation, gene regulation, and gene expression ultimately leading to genomic instability. It induces reactive oxygen species which damage various signaling pathways resulting in abnormal cell division. Autophagy is a natural cell repair process by which damaged cells or cellular components are degraded in the lysosome to maintain homeostasis. Any defect in the autophagy mechanism causes chronic inflammation leading to carcinogenesis. In the arsenic exposed individuals, there is a complete cellular failure by which there is continuous inflammation in the system causing a breach in the defense mechanism. The uncontrolled disease impairment, in the long duration of arsenic exposure, causes failure in the autophagy mechanism causing the disease of cancer in the exposed population.