DNA damage in lung cells in vivo and in vitro by 1,3-butadiene and nitrogen dioxide and their photochemical reaction products

Abstract

A UV-irradiated mixture of 1,3-butadiene and nitrogen dioxide (NO 2) was tested for its potency to induce DNA damage measured as single-strand breaks (SSB) in lungs of mice. Both gases were also tested separately. After 16 h exposure a UV-irradiated mixture of 40 ppm butadiene + 20 ppm NO 2, but not 20 ppm butadiene + 10 ppm NO 2 + UV, induced a significant increase in SSB as measured by the alkaline unwinding technique. There was no increase in the level of SSB using the alkaline elution technique during the same testing conditions. However, after 5 h exposure to 60 ppm butadiene + 30 ppm NO 2 + UV both methods demonstrated a significant increase in SSB. Mice were also exposed to butadiene at 80 and 200 ppm for 16 h and at 500 ppm for 5 h. DNA damage was demonstrated in both liver and lung after 5 and 16 h (only at 200 ppm) of exposure using the unwinding technique. Using the alkaline elution assay, a significant increase in the level of SSB in lung and liver was found only after 5 h of exposure. When mice were exposed to 30 ppm NO 2 for 16 h or 50 ppm for 5 h, a significant increase in SSB was found with the unwinding technique. Alveolar macrophages from mice were also exposed in vitro to the gas mixture and to butadiene and NO 2 separately. In these experiments, the DNA damage was studied with the unwinding technique. A significant effect was demonstrated with 40 ppm butadiene + 20 ppm NO 2 + UV. NO 2 itself contributed to some extent to the increase. Reasons for the discrepancies between the unwinding and the alkaline elution techniques are discussed.