期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：1982
卷号：79
期号：17
页码：5122-5126
DOI：10.1073/pnas.79.17.5122
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Riboflavin 5'-phosphate (flavin mononucleotide; FMN) inhibits the mutagenicity of (+/-)-7 beta, 8 alpha-dihydroxy-9 alpha, 10 alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (B[a]P diol epoxide), the only known ultimate carcinogenic metabolite of benzo[a]pyrene. Coincubation of 10, 25, and 50 nmol of FMN with strain TA100 of histidine-dependent Salmonella typhimurium inhibits the mutagenicity of 0.05 nmol of the diol epoxide by 50, 70, and 90%, respectively. Ribose 5-phosphate and riboflavin show no significant effects at comparable doses. Reaction of B[a]P diol epoxide with FMN in aqueous solution at neutral pH produces only tetraols, with no evidence for covalent adducts. At pH 7 the rate of hydrolysis of B[a]P diol epoxide in dioxane/water, 1:9 (vol/vol), at 25 degrees C is increased more than 10-fold in the presence of 100 muM FMN. Spectrophotometric studies and quantitative rate data for the reaction of the diol epoxide with FMN indicate that a complex is formed between the diol epoxide and the flavin moiety of FMN (Ke = 1,400-3,400 M-1) prior to general acid-catalyzed hydrolysis of the epoxide to tetraols by the phosphate monoanion of FMN. Comparable concentrations of ribose 5-phosphate and riboflavin do not significantly increase the rate of hydrolysis, although evidence for complex formation between riboflavin and the diol epoxide is observed. General acid-catalyzed hydrolysis of bay-region polycyclic hydrocarbon diol epoxides by compounds that have a high affinity for these ultimate carcinogens represents a potentially useful way of inhibiting their carcinogenic activity.
