BACTERIAL AND HUMAN CELL MUTAGENICITY AND MOUSE LUNG TUMORIGENICITY OF THE OXYGENATED POLYNUCLEAR AROMATIC HYDROCARBON PHENALENONE

Phenalenone (perinaphthenone) is a major oxygenated polynuclear aromat ic hydrocarbon (oxy-PAH) atmospheric pollutant formed from the combust ion of fossil fuels, Mutagenicity of phenalenone was measured in quant itative forward mutation assays with Salmonella typhimurium TM677 and metabolically competent human B-lymphoblastoid cell lines (MCL-5 and h 1A1v2 cells), and its tumorigenicity was also assessed in a newborn mo use assay. Phenalenone was mutagenic in Salmonella in the presence of rat liver postmitochondrial supernatant (PMS) at a minimum detectable mutagen concentration (MDMC) of 12 mu g/ml, but was not mutagenic in t he absence of PMS at concentrations up to 100 mu g/ml. Phenalenone was not significantly mutagenic in either human cell line after 28 hr tre atment, although mutant fractions were increased by nearly fivefold in h1A1v2 cells (at the tk lotus) exposed at 30 mu g/ml. However, after 72 hr treatment, phenalenone was mutagenic at the hprt locus in h1A1v2 cells with an MDMC of 3 mu g/ml. Phenalenone was also tumorigenic in male BLU:Ha mice with a lung tumor incidence of 33% 6 months after inj ection with 4.2 mg phenalenone, the highest dose tested, Lung tumor mu ltiplicity in this treatment group was 0.5 tumor/mouse. No increase in lung tumors in female mice was observed, Indices of lung turner incid ence (ED(50)) and multiplicity (TM(1.0)) for male mice were 29.3 and 3 4.9 mu mol, respectively. These data suggest that phenalenone does not contribute significantly to the mutagenicity or carcinogenicity of co mbustion emission extracts. (C) 1996 Society of Toxicology