Diesel Exhaust Particulate Matter Dispersed in a Phospholipid Surfactant Induces Chromosomal Aberrations and Micronuclei but not 6-Thioguanine-Resistant Gene Mutation in V79 Cells

Abstract

Diesel exhaust particulate material (DPM) was assayed for induction of chromosomal aberrations (CA), micronucleus (MN) formation, and 6-thioguanine-resistant (TG^r) gene mutation in V79 cells as a dispersion in dipalmitoyl phosphatidylcholine (DPPC) in physiological saline, a simulated pulmonary surfactant. Filter-collected automobile DPM provided for the study was not organic solvent extracted, but was directly mixed into DPPC in saline dispersion as a model of pulmonary surfactant conditioning of a soot particle depositing in a lung alveolus. A statistically significant difference was found between treated and control groups at all concentrations tested in a CA assay. Assay for MN induction also gave a positive response: Above 50 μg/ml, the frequencies of micronucleated cells (MNC) were about 2 times higher than those in the control group. The forward gene mutation assay did not show a positive response when cells were treated with up to 136 μg DPM/ml for 24 h, as dispersion in DPPC in saline. Some comparison assays were run on direct dispersions of the DPM into dimethyl sulfoxide, with results equivalent to those seen with a DPPC–saline preparation: DPM in dimethyl sulfoxide (DMSO) was positive for MN induction but was negative for forward gene mutation in V79 cells. The positive clastogenicity results are consistent with other studies of DPM dispersed into DPPC–saline surfactant that have shown activity in mammalian cells for sister chromatid exchange, unscheduled DNA synthesis, and MN induction. The forward gene mutation negative results are consistent with studies of that assay applied to V79 cells challenged with DPM solvent extract.

This study was supported in part by the U.S. Department of Energy, National Energy Technology Laboratory, and by the U.S. Department of Energy, FreedomCar and Vechicle Technologies Program. The DPM sample and information on its generation were graciously provided by the Lovelace Respiratory Research Institute, Albuquerque, NM, from studies sponsored by the U.S. Department of Energy under contract DE-AC04-76EV01013. We also thank Michael Kashon of NIOSH for valuable assistance.

Z.-W. Gu is a visiting scientist from Shanghai Institute of Labour Hygiene and Occupational Diseases, Shanghai, People’s Republic of China.

Notes

This study was supported in part by the U.S. Department of Energy, National Energy Technology Laboratory, and by the U.S. Department of Energy, FreedomCar and Vechicle Technologies Program. The DPM sample and information on its generation were graciously provided by the Lovelace Respiratory Research Institute, Albuquerque, NM, from studies sponsored by the U.S. Department of Energy under contract DE-AC04-76EV01013. We also thank Michael Kashon of NIOSH for valuable assistance.

Z.-W. Gu is a visiting scientist from Shanghai Institute of Labour Hygiene and Occupational Diseases, Shanghai, People’s Republic of China.