Impact of Environmental and Occupational Exposures in Reactive Oxygen Species-Induced Pancreatic Cancer

Document Type

Book Chapter

Publication Title

Handbook of Oxidative Stress in Cancer: Mechanistic Aspects

Abstract

One of the deadliest types of human cancer is Pancreatic Cancer (PanCa), owing to its late stage at presentation and pervasive therapeutic resistance. In the USA, by 2020, PanCa is expected to be the second deadliest carcinogenesis. However, this cancer is usually asymptomatic in nature. Chronic pancreatitis, diabetes, and some infectious diseases are important risk factors. Besides these, acquired risk habits, such as smoking and high alcohol intake increase the chance of developing PanCa. Current meta-analysis suggests that the risk of PanCa may be increased by occupational exposures to chlorinated hydrocarbon solvents, organochlorine pesticides, polycyclic aromatic hydrocarbons (PAHs), nickel (Ni), cadmium (Cd), and chromium (Cr). In the digestive system, oxidative stress is known to initiate cancer response. Mitochondrial respiration is one of the key generation machinery, and other environmental and occupational exposures/chemical reagents that induce damage to the DNA, proteins, lipids, and produce many toxic and high mutagenic metabolites that could result in tumor behavior, changing it into a malignant phenotype, and finally in cancer cell transformation. Numerous toxic, carcinogenic, and mutagenic chemical substances along with stable and unstable free radicals and reactive oxygen species (ROS), in the particulate and gas phase of tobacco smoke have the potential of biological oxidation. Several research documentations suggest that carcinogenic compounds in cigarette smoke stimulate cellular proliferation and progression of PanCa by inducing inflammation and fibrosis which results in genetic factors leading to the inhibition of cell death. It has been hypothesized that exposure to one of the occupational risk factors, Cd, a ubiquitous metal, is one of the potential cause of PanCa due to its toxic and carcinogenic properties. Evidence of involvement of Cd in PanCa development has been recently mentioned in our observational studies, meta-analyses, and experimental animal and in vitro studies. Gathering all these previous data, it is clear that oxidative stress-related responses are affected during Cd stress, but the apparent discrepancies observed in between the different research findings point towards the necessity to increase our knowledge on the spatial and temporal ROS signature under Cd stress which is present in different kinds of occupational exposures. Our present effort is to summarize findings in a systematic approach, as to how environmental and occupational risk factors induce ROS generation in PanCa, in addition to its mechanism of action, signalling cascade in the prognosis of the disease.

First Page

637

Last Page

662

DOI

10.1007/978-981-15-9411-3_157

Publication Date

1-1-2022

This document is currently not available here.

Share

COinS