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Light‐dependent mutagenesis by benzo[ a ]pyrene is mediated via oxidative DNA damage
Author(s) -
Kim SuRyang,
Kokubo Kiyoko,
Matsui Keiko,
Yamada Noriyo,
Kanke Yusuke,
Fukuoka Masamichi,
Yamada Masami,
Nohmi Takehiko
Publication year - 2005
Publication title -
environmental and molecular mutagenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1
H-Index - 87
eISSN - 1098-2280
pISSN - 0893-6692
DOI - 10.1002/em.20141
Subject(s) - mutagenesis , dna , dna repair , dna damage , nucleotide excision repair , benzo(a)pyrene , dna glycosylase , carcinogen , chemistry , microbiology and biotechnology , biochemistry , dna adduct , biology , gene , mutation
Benzo[ a ]pyrene (B[ a ]P) is an environmental carcinogenic polycyclic aromatic hydrocarbon (PAH). Mammalian enzymes such as cytochrome P‐450s and epoxide hydrase convert B[ a ]P to reactive metabolites that can covalently bind to DNA. However, some carcinogenic compounds that normally require metabolic activation can also be directly photoactivated to mutagens. To examine whether B[ a ]P is directly mutagenic in the presence of light, we exposed Salmonella typhimurium strains with different DNA repair capacities to B[ a ]P and white fluorescent light at wavelengths of 370–750 nm. B[ a ]P plus light significantly enhanced the number of His + revertants. Mutagenesis was completely light‐dependent and required no exogenous metabolic activation. The order of mutability of strains with different DNA repair capacities was strain YG3001 ( uvrB, mutM ST ) ≫ strain TA1535 ( uvrB ) > strain YG3002 ( mutM ST ) > strain TA1975. The uvrB gene product is involved in the excision repair of bulky DNA adducts, and the mutM ST gene encodes 8‐oxoguanine (8‐oxoG) DNA glycosylase, which removes 8‐oxoG from DNA. Introduction of a plasmid carrying the mOgg1 gene that is the mouse counterpart of mutM ST substantially reduced the light‐mediated mutagenicity of B[ a ]P in strain YG3001. B[ a ]P plus light induced predominantly G:C → T:A and G:C → C:G transversions. We propose that B[ a ]P can directly induce bulky DNA adducts if light is present, and that the DNA adducts induce oxidative DNA damage, such as 8‐oxoG, when exposed to light. These findings have implications for the photocarcinogenicity of PAHs. Environ. Mol. Mutagen., 2005. © 2005 Wiley‐Liss, Inc.