Chemicals act on biological molecules and affect their functions. DNA is one of the most important targets, damaging of which could lead to diverse diseases including cancer. The mode of action of chemicals to DNA contains chemical reaction and protein factor-mediated modulation of the function. In this review, these actions are described in view of effects of chemicals on DNA. First, oxidative damage of DNA is described in several cases of chemicals focusing on its mechanisms involving metals such as copper. We have demonstrated: DNA binding of copper ions prior to reduction-oxidation reaction is crucial for the damaging, probably due to the proximal attack of reactive oxygen species; reduction of the bound copper induces a conformational change of DNA strand through rearrangement of copper-coordination geometry; RNA, another nucleic acid, is more liable to oxidative damage than DNA. Impact of RNA damage on oxidative stress-related diseases is discussed. Second, a group of chemicals called endocrine disruptors is described. Phthalate esters are ubiquitous endocrine disruptors of which mechanisms are still elusive. Here, we present our research performed for elucidation of the active metabolite and molecular target. Novel candidates of active metabolite are suggested. Finally, toxicological activity dynamics are described, showing several chemicals exert toxic potential by structural alteration in the environment, metabolism, or both. These imply gene-environment interactions that would underlie various diseases induced by environmental chemicals.