Comparison of the mutational specificity induced by environmental genotoxin nitrated polycyclic aromatic hydrocarbons in Salmonella typhimurium his genes

Abstract Mutagenicity of 15 nitrated polycyclic aromatic hydrocarbons (nitro-PAHs), which were detected in ambient air particles and/or combustion source emissions, were examined using a set of six Salmonella typhimurium tester strains (TA7001 to TA7006), and the mutational specificity was characterized by the comparison of the mutagenic potencies of nitro-PAHs in the tester strains. Each strain carries a unique missense mutation in the histidine operon and is reverted by only one specific base-substitution out of six possible changes. All nitro-PAHs tested were mutagenic in multiple strains, and were classified into four categories based on the strains predominantly reverted. 1-Nitropyrene (1-NPy), 2,7-dinitrofluoren-9-one and 1,3-, 1,6- and 1,8-dinitropyrene isomers exerted the highest mutagenicity in strain TA7005 (C·G→A·T transversion) followed by strain TA7006 (C·G→G·C transversion). 2- And 3-nitrofluoren-9-one isomers, 2-NPy and 2,7-dinitrophenanthrene were also markedly mutagenic in strain TA7005 but not in strain TA7006. For 2-, 3- and 9-nitrophenanthrene isomers, 2-nitrofluoranthene (2-NFT) and 4-NPy, TA7004 (G·C→A·T transition) was the most responsive strain. 3-NFT was unique, showing the highest mutagenicity in strain TA7002 (T·A→A·T transversion). All nitro-PAHs tested induced C·G→A·T transversion, which is observed as the most frequent base-substitution mutation of p53 tumor suppressor gene in human lung cancer.