© 1996 Oxford University Press
research-article |
Bacterial and Human Cell Mutagenicity and Mouse Lung Tumorigenicity of the Oxygenated Polynuclear Aromatic Hydrocarbon Phenalenone
Division of Toxicology and Center for Environmental Health Sciences Massachusetts Institute of Technology, Cambridge, Massachusetts 02139
Received January 16, 1996; accepted May 23, 1996
Phenalenone (perinaphthenone) is a major oxygenated polynuclear aromatic hydrocarbon (oxy-PAH) atmospheric pollutant formed from the combustion of fossil fuels. Mutagenicity of phenalenone was measured in quantitative forward mutation assays with Salmonella typhimurium TM677 and metabolically competent human B-lymphoblastoid cell lines (MCL-5 and hlAlv2 cells), and its tumorigenicity was also assessed in a newborn mouse assay. Phenalenone was mutagenic in Salmonella in the presence of rat liver postmitochondrial supernatant (PMS) at a minimum detectable mutagen concentration (MDMC) of 12 /µg/ml, but was not mutagenic in the absence of PMS at concentrations up to 100 /µg/ ml. Phenalenone was not significantly mutagenic in either human cell line after 28 hr treatment, although mutant fractions were increased by nearly fivefold in hlAlv2 cells (at the tk locus) exposed at 30 µg/ml. However, after 72 hr treatment, phenalenone was mutagenic at the hprt locus in hlAlv2 cells with an MDMC of 3 µg/ml Phenalenone was also tumorigenic in male BLU:Ha mice with a lung tumor incidence of 33% 6 months after injection with 4.2 mg phenalenone, the highest dose tested. Lung tumor multiplicity in this treatment group was 0.5 tumor/mouse. No increase in lung tumors in female mice was observed. Indices of lung tumor incidence (ED50) and multiplicity (TM1.0) for male mice were 29.3 and 34.9 µxmol, respectively. These data suggest that phenalenone does not contribute significantly to the mutagenicity or carcinogenicity of combustion emission extracts.