Benzo[c]chrysene, dibenz[a,j]anthracene, and dibenz[a,h]anthracene diol epoxides: Mutation spectra in S. typhimurium and E. coli CLP systems

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental pollutants. These pollutants metabolize to reactive dihydrodiol epoxides that react with DNA and cause damages, which may lead to mutations and initiation of tumors. In light of the problems PAHs pose to humans, knowing the mutation spectra of the dihydrodiol epoxides may help to determine if a given PAH contributes to the tumors seen in humans. Toward this end, the mutation spectra of the dihydrodiol isomers of benzo[c]chrysene and dibenz[a,j]anthracene in Salmonella typhimurium strains TA7001-TA7006 and E. coli CLP strains CL 101P-CL106P were determined. The mutation spectra of the dihydrodiol epoxides of dibenz[a,h]anthracene were determined, but only in the E. coli CLP system. In Salmonella, G·C → T·A transversions were the predominant mutations observed for the (+)-anti-B[c]CDE, (+)-syn-B[c]CDE, and (-)-syn-B[c]CDE isomers, whereas G·C → A·T transitions were the predominant mutations found for (-)-anti-B[c]CDE. The predominant mutations in Salmonella for (-)-anti-DB[a,j]ADE, and (+)-syn-DB[a,j]ADE were G·C → T·A transversions, whereas for (+)-anti-DB[a,j]ADE and (-)-syn-DB[a,j]ADE the predominance of G·C → C·G changes were noted. In E. coli, all B[c]CDEs, DB[a,j]ADEs, and DB[a,h]ADEs predominantly induced G·C → T·A transversions. In both bacterial systems, the mutation spectra of B[c]CDEs, DB[a,j]ADEs, and DB[a,h]ADEs showed preferential induction of mutations at G·C base pairs. For B[c]CDEs and DB[a,j]ADEs, for which DNA binding properties and adduct distributions at dG vs dA were known, the results correlated with these diol epoxides' preferences for adduct formation at dG residues in DNA. At A·T base pairs, A·T → T·A transversions were the changes most frequently induced. For the most part, B[c]CDEs, DB[a,j]ADEs, and DB[a,h]ADEs induced G·C → T·A transversions, the type of mutations commonly found in the p53 gene in human tumors. Therefore, given the prevalence of the parent compounds of these diol epoxides in the environment and the known association of other PAHs with p53 mutation in lung cancer, it is conceivable the diol epoxides of B[c]C, DB[a,j]A, and DB[a,h]A contribute to lung cancer in humans.