title: 9,10-Phenanthrenequinone induces DNA deletions and forward mutations via oxidative mechanisms in the yeast Saccharomyces cerevisiae.
abstract: The estimated cancer risk from diesel exhaust particles (DEP) in the air is approximately 70% of the cancer risk from all air pollutants. DEP is comprised of a complex mixture of chemicals whose carcinogenic potential has not been adequately assessed. The polycyclic aromatic hydrocarbon quinone 9,10-phenanthrenequinone (9,10 PQ) is a major component of DEP and a suspect genotoxic agent for DEP induced DNA damage. 9,10 PQ undergoes redox cycling to produce reactive oxygen species that can lead to oxidative DNA damage. We used two systems in the yeast Saccharomyces cerevisiae to examine possible differential genotoxicity of 9,10 PQ. The DEL assay measures intra-chromosomal homologous recombination leading to DNA deletions and the CAN assay measures forward mutations leading to canavanine resistance. Cells were exposed to 9,10 PQ aerobically and anaerobically followed by DNA damage assessment. The results indicate that 9,10 PQ induces DNA deletions and point mutations in the presence of oxygen while exhibiting negligible effects anaerobically. In contrast to the cytotoxicity observed aerobically, the anaerobic effects of 9,10 PQ seem to be cytostatic in nature, reducing growth without affecting cell viability. Thus, 9,10 PQ requires oxygen for genotoxicity while different toxicities exhibited aerobically and anaerobically suggest multiple mechanisms of action.
authors.affiliation: Department of Pharmacology, Geffen School of Medicine, Center for the Health Sciences, Los Angeles, CA 90095-1735, USA.
authors.forename: Chester E
authors.initials: CE
authors.lastname: Rodriguez
authors.forename: Zhanna
authors.initials: Z
authors.lastname: Sobol
authors.forename: Robert H
authors.initials: RH
authors.lastname: Schiestl
mesh_terms: D000332:Aerobiosis; D000693:Anaerobiosis; D016227:Benzoquinones / Q000494:pharmacology; D002172:Canavanine / Q000494:pharmacology; D004249:DNA Damage / Q000187:drug effects; D004271:DNA, Fungal / Q000187:drug effects* / Q000235:genetics*; D017353:Gene Deletion; D009153:Mutagens / Q000633:toxicity*; D009154:Mutation / Q000187:drug effects*; D010084:Oxidation-Reduction; D010616:Phenanthrenes / Q000633:toxicity*; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics*
chemical_list: D016227:Benzoquinones; D004271:DNA, Fungal; D009153:Mutagens; D010616:Phenanthrenes; D002172:Canavanine; C004532:quinone; C005399:9,10-phenanthrenequinone