P-450 and Chemical Carcinogenesis

This book is one of a GANN Monograph on Cancer Research series and is based on a Japanese Cancer Association-sponsored symposium entitled "Multiplicity of Chemical Carcinogen-Activating Enzymes· with Particular Emphasis on Cytochrome P-450" which was held in Tokyo on November 21, 1983. The principal role of microsomal cytochrome P-450 in the metabolic activation of various chemical carcinogens in animal cells has been well established. The activated chemical carcinogens induce mutations of the cells, which is an essential part of the initiation of chemical carcinogenesis. Since microsomal cytochrome P-450 in various animal tissues includes multiple molecular species with different substrate specificities and different responses to chemical inducers, knowledge of the molecular and catalytic properties and the inducibilities of those cytochrome P-450 forms is surely a most important base from which to elucidate the mechanism of chemical carcinogenesis. The focus of the symposium was this area of molecular diversity and inducibility of microsomal cytochrome P-450 in animal tissues. The mechanism of activation of various types of chemical carcinogens by cytochrome P-450 and related enzymes was another main topic. The editors, who were also the symposium organizers, hope these summaries of current research in this field in Japan will stimulate future development of studies on the mechanism of chemical carcinogenesis.