Molecular Mechanisms of Toxic Chemicals

Abstract

Most human cancers are caused by toxic organic or inorganic chemicals. Environmental exposure allows these chemicals to enter the body and almost every body cell. Within the body cells, five multi-enzyme systems process these chemicals. The chemicals can be activated to their ultimate carcinogenic molecular structures (usually to free radicals) or they can generate free radicals from water molecules. As electrophilic radicals, they can attack and co-valently bind to guanine in G-C or other DNA base pair units within the chromosomes resulting in genomic alterations, possibly in mutations. As protection against this, the radicals can be inactivated and any altered/mutated genes may be repaired. The five carcinogen-processing systems contain more than 300 enzymes. Each enzyme is coded from inherited genes. Therefore, one inherits high versus low genetic susceptibility to the processing of toxic chemicals and the repair of damaged genes through these intracellular carcinogen-processing enzyme systems. Hence, carcinogenesis is a multifactorial process based on both environmental and genetic factors.