Comparative oncogenic activation of 7H-dibenzo[c,g]carbazole and dibenze[a,j]acridine

被引:0
|
作者
Warshawsky, D [1 ]
Mitchell, K [1 ]
Xue, WL [1 ]
Jaeger, M [1 ]
Schneider, J [1 ]
Talaska, G [1 ]
机构
[1] Univ Cincinnati, Dept Environm Hlth, Cincinnati, OH 45267 USA
关键词
7H-dibenzo[c; g]carbazole; dibenz[a; j]acridine; oncogenic activation; oncogenes; ras;
D O I
10.1080/10406639908020584
中图分类号
O62 [有机化学];
学科分类号
070303 ; 081704 ;
摘要
7H-Dibenzo[c,g]carbazole (DBC) is a potent liver, lung and skin carcinogen while dibenz[a,j]acridine (DBA) is a moderate skin carcinogen. DEC is metabolized to phenols and DBC-DNA adducts are formed through the 2-, 3-, and 4-phenols or directly through radical cations. Mutations in ras as a result of DEC, activation are found exclusively in codon 61 in liver, lung and skin. DBA is metabolized to dihydrodiols, and phenols and DBA-DNA adducts are formed through the diol-epoxides and possibly through bis-diol-epoxides. Mutations in ras, as a result of DBA activation, are found in codons 12, 13, and 61. These results indicate that although the two compounds are structurally similar, differing by one carbon in the middle ring, there are differences in their metabolism, DNA binding, mutational spectra and target-organ carcinogenesis.
引用
收藏
页码:173 / 179
页数:7
相关论文
共 50 条
  • [41] HUMAN CELL-MEDIATED CYTO-TOXICITY AND MUTAGENICITY OF THE NITROGEN HETEROCYCLIC 7H-DIBENZO(C,G)CARBAZOLE(DBC)
    PARKS, WC
    MAHER, VM
    MCCORMICK, JJ
    ENVIRONMENTAL MUTAGENESIS, 1984, 6 (03): : 475 - 475
  • [42] MUTAGENICITY OF 7H-DIBENZO(C,G)CARBAZOLE AND ITS METABOLITES IN A CHINESE-HAMSTER EPITHELIAL-CELL LINE AND SALMONELLA
    DOOLEY, J
    SCHOENY, R
    CHRISTIAN, R
    WARSHAWSKY, D
    ENVIRONMENTAL MUTAGENESIS, 1982, 4 (03): : 330 - 331
  • [43] ACETYLATION OF PHENOLIC DERIVATIVES OF 7H-DIBENZO[C,G]CARBAZOLE - IDENTIFICATION AND QUANTITATION OF MAJOR METABOLITES BY RAT-LIVER MICROSOMES
    XUE, WL
    SCHNEIDER, J
    JAYASIMHULU, K
    WARSHAWSKY, D
    CHEMICAL RESEARCH IN TOXICOLOGY, 1993, 6 (03) : 345 - 350
  • [44] TISSUE DISTRIBUTION OF DNA-ADDUCTS OF 7H-DIBENZO[C,G]CARBAZOLE AND ITS DERIVATIVES IN MICE FOLLOWING TOPICAL APPLICATION
    TALASKA, G
    REILMAN, R
    SCHAMER, M
    ROH, JH
    XUE, W
    FREMONT, SL
    WARSHAWSKY, D
    CHEMICAL RESEARCH IN TOXICOLOGY, 1994, 7 (03) : 374 - 379
  • [45] The effects of a binary mixture of benzo(a)pyrene and 7H-dibenzo(c,g)carbazole on lung tumors and K-ras oncogene mutations in strain A/J mice
    Gray, DL
    Warshawsky, D
    Xue, WL
    Nines, R
    Wang, Y
    Yao, RS
    Stoner, GD
    EXPERIMENTAL LUNG RESEARCH, 2001, 27 (03) : 245 - 253
  • [46] One-electron oxidation is not a major route of metabolic activation and DNA binding for the carcinogen 7H-dibenzo [c,g] carbazole in vitro and in mouse liver and lung
    Dowty, HV
    Xue, WL
    LaDow, K
    Talaska, G
    Warshawsky, D
    CARCINOGENESIS, 2000, 21 (05) : 991 - 998
  • [47] THE RESPONSE OF CULTURED CHINESE-HAMSTER CELLS (DPI-3) AND SALMONELLA TO 7H-DIBENZO (C,G) CARBAZOLE AND ITS METABOLITES
    DOOLEY, J
    SCHOENY, R
    WARSHAWSKY, D
    CHRISTIAN, R
    YERGANIAN, G
    IN VITRO-JOURNAL OF THE TISSUE CULTURE ASSOCIATION, 1982, 18 (03): : 300 - 300
  • [48] P-32 POSTLABELING ANALYSIS OF DNA ADDUCTION IN MICE BY SYNTHETIC METABOLITES OF THE ENVIRONMENTAL CARCINOGEN, 7H-DIBENZO[C,G]CARBAZOLE - CHROMATOGRAPHIC EVIDENCE FOR 3-HYDROXY-7H-DIBENZO[C,G]CARBAZOLE BEING A PROXIMATE GENOTOXICANT IN LIVER BUT NOT SKIN
    SCHURDAK, ME
    STONG, DB
    WARSHAWSKY, D
    RANDERATH, K
    CARCINOGENESIS, 1987, 8 (04) : 591 - 597
  • [49] The role of human cytochrome P4503A4 in biotransformation of tissue-specific derivatives of 7H-dibenzo[c,g]carbazole
    Mesarosova, Monika
    Valovicova, Zuzana
    Srancikova, Annamaria
    Krajcovicova, Zdenka
    Milcova, Alena
    Sokolova, Romana
    Schmuczerova, Jana
    Topinka, Jan
    Gabelova, Alena
    TOXICOLOGY AND APPLIED PHARMACOLOGY, 2011, 255 (03) : 307 - 315
  • [50] Synthesis of depurinating DNA adducts formed by one-electron oxidation of 7H-dibenzo[c,g]carbazole and identification of these adducts after activation with rat liver microsomes
    Chen, L
    Devanesan, PD
    Byun, J
    Gooden, JK
    Gross, ML
    Rogan, EG
    Cavalieri, EL
    CHEMICAL RESEARCH IN TOXICOLOGY, 1997, 10 (02) : 225 - 233