Combined exposure to NO 2, O 3 and H 2SO 4-aerosol and lung tumor formation in rats

Abstract

The promoting effects of a combined exposure to two pollutants (NO 2, O 3 or H 2SO 4-aerosol) at near ambient levels on lung tumorigenesis induced by N-bis(2-hydroxypropyl) nitrosamine (BHPN) were investigated in male Wistar rats. The rats were given a single intraperitoneal injection of BHPN (0.5 g per kg body wt.) at 6 weeks of age. They then were exposed to clean air, 0.05 ppm O 3 (mean concentration for 10 h/day; 0.1 ppm peak concentration), 0.05 ppm O 3 (mean concentration for 10 h/day; 0.1 ppm peak concentration) + 0.4 ppm NO 2 or 0.4 ppm NO 2 + 1 mg/m 3 of H 2SO 4-aerosol for 13 months and were then maintained in a clean room for another 11 months. Room control animals were kept after injection of BHPN in a clean room for 24 months. The incidence of primary lung tumors in rats exposed to 0.05 ppm O 3, 0.05 ppm O 3 + 0.4 ppm NO 2 and 0.4 ppm NO 2 + 1 mg/m 3 of H 2SO 4-aerosol with BHPN treatment was 8.3% (3 out of 36 rats), 13.9% (5 out of 36 rats) and 8.3% (3 out of 36 rats), respectively. The tumors were adenomas and adenocarcinomas. The incidence of adenomas was 2.8% (1 out of 36 rats) in the O 3 alone group, 11% (4 out of 36 rats) in O 3 + NO 2 group and 5.6% (2 out of 36 rats) in NO 2 + H 2SO 4 group. The incidence of adenocarcinomas was 5.6% (2 out of 36 rats) in the O 3 group, 2.8% (1 out of 36 rats) in O 3 + NO 2 group and 2.8% (1 out of 36 rats) in NO 2 + H 2SO 4 group. No lung tumors were found in the rats exposed to clean air with BHPN treatment and in animals not given BHPN but exposed to each air pollutant. The difference in tumor incidence between the clean air group with BHPN and the O 3 + NO 2 group with BHPN was statistically significant. The results show that exposure to O 3 alone enhances tumor development and that the combined exposure to O 3 or H 2SO 4 with NO 2 produces an additional increase in incidence of lung tumor, respectively. The incidence of slight-moderate to marked alveolar cell hyperplasia in the groups exposed to each air pollutant with BHPN treatment was higher than that in the groups exposed to clean air with BHPN. Exposure to each air pollutant had no effect on the development of bronchiolar mucosal hyperplasia in lungs of rats treated with BHPN. These results suggest that the exposure to O 3 + NO 2 or NO 2 + H 2SO 4 even at ambient levels of each pollutant may have a synergistic action as a tumor promoter and that free radical generation and lipid peroxide production by exposure to those air pollutants may be related to lung tumor promotion.