ABSTRACT
Many chemicals require initial metabolic activation to electrophilic intermediates in order to exert carcinogenic effects. This phase 1 reaction is mostly catalyzed by the cytochrome P450 (CYP) superfamily. If not subsequently inactivated by phase 2 conjugation reactions, electrophiles can interact with DNA, form DNA adducts, and cause genetic lesions. The phase 2 reactions include those catalyzed by various enzymes, particularly glutathione transferases (GSTs), which are recognized to play a major role in inactivation of carcinogens. Activation of chemicals can also lead to generation of reactive oxygen species (ROS) that will oxidize DNA. If not repaired, these different DNA lesions can be carcinogenic.
