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.
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页码:173 / 179
页数:7
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