Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
, 46 (3), 141-9

Light-dependent Mutagenesis by Benzo[a]pyrene Is Mediated via Oxidative DNA Damage

Affiliations

Light-dependent Mutagenesis by Benzo[a]pyrene Is Mediated via Oxidative DNA Damage

Su-Ryang Kim et al. Environ Mol Mutagen.

Abstract

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, mutMST) >> strain TA1535 (uvrB) > strain YG3002 (mutMST) > strain TA1975. The uvrB gene product is involved in the excision repair of bulky DNA adducts, and the mutMST 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 mutMST 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.

Similar articles

See all similar articles

Cited by 1 PubMed Central articles

  • Thresholds of Genotoxic and Non-Genotoxic Carcinogens
    T Nohmi. Toxicol Res 34 (4), 281-290. PMID 30370002. - Review
    Exposure to chemical agents is an inevitable consequence of modern society; some of these agents are hazardous to human health. The effects of chemical carcinogens are of …

Publication types

MeSH terms

LinkOut - more resources

Feedback