The mode of action of organic carcinogens on cellular structures.
Most genotoxic organic carcinogens require metabolic activation to exert their detrimental effects. The present review summarizes the mechanisms of how organic carcinogens are bioactivated into DNA-reactive descendants. Beginning with the history of discovery of some important human organic carcinogens, the text guides through the development of the knowledge on their molecular mode of action that has grown over the past decades. Some of the most important molecular mechanisms in chemical carcinogenesis, the role of the enzymes involved in bioactivation, the target gene structures of some ultimate carcinogenic metabolites, and implications for human cancer risk assessment are discussed.
Luch
Andreas
A
Massachusetts Institute of Technology, Center for Cancer Research, 77 Massachusetts Avenue, E17-132, Cambridge, Massachusetts 02319, USA. luch@mit.edu
D001711:Biotransformation; D002273:Carcinogens / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D022082:Cellular Structures / Q000187:drug effects*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004249:DNA Damage; D006801:Humans; D015394:Molecular Structure; D009369:Neoplasms / Q000139:chemically induced*; D013329:Structure-Activity Relationship
D002273:Carcinogens; D003577:Cytochrome P-450 Enzyme System