Env_tox_lecture3_2010课件.pptVIP

Carcinogenic activation of 2-naphthylamine Precarcinogens Dichloroethane Waste product of vinyl chloride production and also a laboratory solvent Its analog, dichloromethane, is used as a gasoline additive and as an insecticide Carcinogen and mutagens Conjugate with glutathione to form haloethyl-S-glutathione which is structurally similar to sulfur mustard, used as war gas during world war I Haloethyl-S-glutathione spontaneously forms an unstable three-member ring that, upon ring opening, reacts with cellular macromolecules. Carcinogenic activation of 1.2-dichloroethane Precarcinogens Vinyl chloride Starting materials in the manufacture of poly(vinyl chloride) plastics Associated with high frequency of angiosarcoma, a rare liver cancer. Carcinogenic activation Involves epoxide formation Carcinogenic activation and further metabolism of vinyl chloride Precarcinogens Aflatoxins 黄曲霉毒素 Produced by a mold, Aspergillus flavus Contaminates crops such as corn and peanuts Aflatoxin B1 : can be metabolized by cytochrome P-450 to a carcinogen Carcinogenic activation of aflatoxin B1 Precarcinogens Benzo[?]pyrene A major polycyclic hydrocarbon carcinogen in the environment Occurs in industrial smoke, cigarette smoke and tar, and in fried, broiled, or smoked food. Metabolized by P-450 to form an epoxides, 7,8-dihydrodiol-9,10-trans-epoxide that is a carcinogen with half-life of 8 min. It is probably long enough to react with DNA. Carcinogenic activation of benzo[?]pyrene Precarcinogens Nitrosamines亚硝胺 Formed by the reaction of nitrite ions with secondary and tertiary amines, e.g. dimethylamine used in rubber, leather and soap manufacturing The formation of carcinogenic nitrosamines can be prevented by compounds that compete with secondary and tertiary amines for the nitrite ion, e.g. primary amines, ascorbic acid and tocopherol. Carcinogenic activation of dimethylamine by reaction with nitrite ions * * Environmental Health and Toxicology Chapter 3 Metabolism of Xenobiotics