The effects of
nitrogen dioxide (NO2) on promotion of lung
tumorigenesis induced by N-bis(2-hydroxypropyl)
nitrosamine (
BHPN) were investigated in male Wistar rats. In a preliminary study, the highest non-effective dose of
BHPN was found to be 0.5 g per kg
body weight. Rats were given a single
intraperitoneal injection of
BHPN at a dose of 0.5 g 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 of NO2 for 17 months, respectively. The incidence of pulmonary
tumors in rats exposed to
BHPN plus 4 ppm of NO2 was 12.5%; the
tumors were
adenomas and
adenocarcinomas.
Adenomas were found in 4 out of 40 rats (10%) and
adenocarcinomas were found in 1 out of 40 rats (2.5%). The
tumor incidence in the lungs of rats kept in
BHPN plus clean air and
BHPN plus 0.04 ppm of NO2 was 2.5% (1/40). In both groups
adenomas were found. There was no significant difference in
tumor incidence between animals exposed to
BHPN plus clean air and to
BHPN plus 4 ppm of NO2. No lung
tumors were found in the group of
BHPN plus 0.4 ppm NO2 and in animals exposed to NO2 without
BHPN treatment. A high incidence of alveolar cell
hyperplasia was observed in the lungs of rats injected with
BHPN, and the effect of NO2 on development of alveolar cell
hyperplasia was slight. On the other hand, marked bronchiolar mucosal
hyperplasia was found in 17 out of 40 rats (42.5%) in the group of
BHPN plus 4 ppm of NO2, and in 1 out of 40 rats (2.5%) in each of the group exposed to clean air, 0.04 ppm or 0.4 ppm of NO2 with
BHPN treatment, respectively. The
hyperplasia in lungs of rats exposed to 4 ppm of NO2 without
BHPN treatment was slighter than that in lung of rat exposed to 4 ppm of NO2 with
BHPN treatment. On the other hand,
tumor incidence in the nasal cavity of rats in each of group exposed to clean air and NO2 with
BHPN treatment was 97-100%. Incidence of
tumors in other organs in the groups exposed to clean air and NO2 with and without
BHPN treatment was very low, and NO2 had no effect on
tumor development in the nasal cavity and other organs whether animals were treated with
BHPN or not.(ABSTRACT TRUNCATED AT 400 WORDS)