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标题：Pyrolysis products from amino acids and protein: Highest mutagenicity requires cytochrome P1-450
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作者：Daniel W. Nebert ; Sanford W. Bigelow ; Allan B. Okey 等
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：1979
卷号：76
期号：11
页码：5929-5933
DOI：10.1073/pnas.76.11.5929
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Pyrolysis products of proteins and amino acids are highly mutagenic, but metabolism of these chemicals by rat liver subcellular fractions is known to be required for production of the mutagenic intermediates. We examined the mutagenesis of seven purified pyrolysis products from tryptophan, lysine, glutamic acid, and soybean globulin with Salmonella typhimurium strain TA98 in the presence of liver fractions from genetically "responsive" C57BL/6N and Ahb/Ahd or "nonresponsive" DBA/2N and Ahd/Ahd mice that had been pretreated in vivo with benzo[a]pyrene. For all pyrolysis products tested, mutagenesis is 2-fold to more than 1000-fold greater with C57BL/6N and Ahb/Ahd than with DBA/2N or Ahd/Ahd liver fractions. A sucrose density gradient assay for detecting the Ah regulatory gene product, the receptor, was studied with C57BL/6N hepatic cytosol. At levels 100 times in excess of [1,6-3H]2,3,7,8-tetrachlorodibenzo-p-dioxin, nonlabeled 2,3,7,8-tetrachlorodibenzo-p-dioxin, 3-methylcholanthrene, and {beta}-naphthoflavone (inducers of cytochrome P1-450) are able to displace the radioligand from its hepatic cytosolic receptor; four pyrolysates from tryptophan, glutamic acid, and soybean globulin did not have this capacity. These data indicate that the pyrolysis products tested, although not effective as inducers of cytochrome P1-450, are most mutagenic when metabolized by P1-450. Potent P1-450 inducers--present in pyrolysates during the combustion process--might be present in quantities insufficient to initiate mutagenesis or carcinogenesis but might have a synergistic action, or act as "comutagens" or "cocarcinogens," with the N-containing heterocyclic pyrolysis products. A quantitative relationship between mutagenic and carcinogenic potency of these pyrolysis products remains, however, to be demonstrated.
关键词：environmental mutagenesis ; chemical carcinogenesis ; cigarette smoking ; cytochrome P -450-mediated monooxygenase ; metabolic activation