Comparative Oncogenic Activation of 7H-Dibenzo[C, G]Carbazole and Dibenz[A, J]Acridine

Abstract

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. DBC 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 DBC, 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.