Effects of Nitrogen Dioxide Exposure on Pulmonary Metastasis of Walker-256 Tumor

Abstract

Nitrogen dioxide (NO2), one of the most common air pollutants, is known to have toxic effects on the respiratory tract, and is also considered to be a mutagen. To study the relationship between NO2 and tumor growth or pulmonary metastasis, female 7-weekold Wistar-Imamichi strain rats were made to inhale 5 or 0.5 ppm NO₂ for 1, 5, 14 days before, and 1, 5 days after inoculation of 3 × 106 Walker-256 tumor cells into their tail veins (IV) or subcutaneous tissues (SC).No effect was seen on SC tumor growth, but in rats that inhaled NO2 for one day followed by IV injection of tumor cells (5 ppm BI-1 group), 13 days after IV, pulmonary metastasis was significantly increased when evaluated by Ridit analysis. These tumor cells showed higher BrdU labelling index, and the most invasive growth on histological examination. One day after IV, the 5 ppm BI-1 group showed peribronchiolar invasion Tumor growth was limited to intra- and perivascular areas in all other groups. The 5 ppm BI-1 group showed bronchiolar and peribronchiolar inflammation and perivascular edema before tumor cell inoculation, and BALF study revealed higher numbers of neutrophils and lymphocytes.
NO₂ exposure enhanced pulmonary metastasis of Walker-256 tumor, and the major cause of enhancement was supposed to be due to injury of the pulmonary vasculature by NO₂ exposure.