DNA-DAMAGE IN LUNG-CELLS IN-VIVO AND IN-VITRO BY 1,3-BUTADIENE AND NITROGEN-DIOXIDE AND THEIR PHOTOCHEMICAL-REACTION PRODUCTS

A UV-irradiated mixture of 1,3-butadiene and nitrogen dioxide (NO2) wa s tested for its potency to induce DNA damage measured as single-stran d breaks (SSB) in lungs of mice. Both gases were also tested separatel y. After 16 h exposure a UV-irradiated mixture of 40 ppm butadiene + 2 0 ppm NO2, but not 20 ppm butadiene + 10 ppm NO2 + UV, induced a signi ficant 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 expo sure to 60 ppm butadiene + 30 ppm NO2 + UV both methods demonstrated a significant increase in SSB. Mice were also exposed to butadiene at 8 0 and 200 ppm for 16 h and at 500 ppm for 5 h. DNA damage was demonstr ated in both liver and lung after 5 and 16 h (only at 200 ppm) of expo sure 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 NO2 for 16 h or 50 ppm for 5 h, a significant increase in SSB was found with t he unwinding technique. Alveolar macrophages from mice were also expos ed in vitro to the gas mixture and to butadiene and NO2 separately. Ln these experiments, the DNA damage was studied with the unwinding tech nique. A significant effect was demonstrated with 40 ppm butadiene + 2 0 ppm NO2 + UV. NO2 itself contributed to some extent to the increase. Reasons for the discrepancies between the unwinding and the alkaline elution techniques are discussed.