The effects of nitrogen dioxide (NO
2) on lung tumorigenesis by N-bis (2-hydroxypropyl) nitrosamine (DHPN) in male Wistar rats were investigated. Rats were given a single intraperitoneal injection of 0.5 g DHPN per kg body weight or saline at 6 weeks of age, and then exposed to clean air, 0.04 ppm, 0.4 ppm or 4 ppm NO
2 for 17 months. Incidence of tumor in lungs of rats in DHPN+4 ppm NO
2 group was 13%, and the tumors were adenoma and adenocarcinoma. Adenoma was seen in 4 of 40 rats (10%) and adenocarcinoma was seen in 1 of 40 rats (3%). The incidence of tumor in lungs of rats in DHPN+ clean air and DHPN+0.04 ppm NO
2groups was 3%(1/40), respectively. The tumors were adenoma. There was no significant difference in the incidence of tumors between DHPN+clean air group and DHPN-I-4 ppm NO
2 group. No lung tumor was seen in DHPN-I-0.4 ppm group and each NO
2-exposed group without DHPN treatment. Alveolar cell hyperplasia occurred at the highest incidence in lungs of rats injected with DHPN. But, there was no correlation between the incidence of hyperplasia and each concentration of NO
2 exposed. Bronchiole mucosal hyperplasia was seen in 17 of 40 rats (43%) in the DHPN+4 ppm NO2 group, and in 1 of 40 rats (3%) in the each clean air, 0.04 ppm or 0.4 ppm NO2-exposed group with DHPN treatment. The hyperplasia in lungs of rats exposed to 4 ppm NO
2 without DHPN treatment was slighter than that seen in the 4 ppm NO
2-exposed group with DHPN treatment.
These results indicate that development of lung tumors in rats injected with subcarcinogenic dose of DHPN was enhanced by exposure to 4 ppm NO
2. However, low levels of NO
2 effect on lung tumor development was not observed in Wistar rats.
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