The promoting effects of a combined exposure to two
pollutants (NO2, O3 or H2SO4-
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 O3 (mean concentration for 10 h/day; 0.1 ppm peak concentration), 0.05 ppm O3 (mean concentration for 10 h/day; 0.1 ppm peak concentration) + 0.4 ppm NO2 or 0.4 ppm NO2 + 1 mg/m3 of H2SO4-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 O3, 0.05 ppm O3 + 0.4 ppm NO2 and 0.4 ppm NO2 + 1 mg/m3 of H2SO4-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 O3 alone group, 11% (4 out of 36 rats) in O3 + NO2 group and 5.6% (2 out of 36 rats) in NO2 + H2SO4 group. The incidence of
adenocarcinomas was 5.6% (2 out of 36 rats) in the O3 group, 2.8% (1 out of 36 rats) in O3 + NO2 group and 2.8% (1 out of 36 rats) in NO2 + H2SO4 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 O3 + NO2 group with
BHPN was statistically significant. The results show that exposure to O3 alone enhances
tumor development and that the combined exposure to O3 or H2SO4 with NO2 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.(ABSTRACT TRUNCATED AT 400 WORDS)