Chemicals and Cancer

Abstract

Cancer is a deadly yet diverse condition featuring the emergence of cell subtypes that escape normal restraints on proliferation, forming cellular masses possessing unstable genomes and aggressive tendencies to invade local tissue or metastasise to remote sites. Since the accumulation of mutations in critical genes typically underpins these harmful capabilities, modern toxicology devotes much effort to identifying chemicals that cause mutations. Particular attention focusses on the mechanisms whereby bioactivation-dependent carcinogens form DNA-reactive metabolites that generate abnormal bases within the genome. Such ‘DNA adducts’ are central to chemical carcinogenesis since they can either generate mutations during processing by DNA polymerases, trigger apoptosis or undergo enzymatic repair. DNA adducts are also useful biomarkers of carcinogen exposure in humans and animals. These concepts are reinforced by studying the toxicology of known human carcinogens (e.g. vinyl chloride, asbestos and aristolochic acid) as well as chemicals with a still unclear role in human cancer (e.g. acrylamide).