Rk. Sindhu et al., EFFECT OF CHRONIC EXPOSURE TO OZONE AND NITRIC-ACID ON CYTOCHROME-P-450 MONOOXYGENASE SYSTEM OF RAT LUNG AND LIVER, Inhalation toxicology, 8(7), 1996, pp. 695-708
Male F344/N rats were exposed to 0.15 ppm ozone (O-3) and 50 mu g/m(3)
nitric acid (HNO3) vapor alone and in combination for 4 h/day, 3 days
/wk for a total of 40 wk to investigate the effects of these environme
ntal pollutants on cytochrome P-450 monooxygenases in pulmonary and he
patic microsomes. Exposure to HNO3 vapor alone caused a significant in
crease of 7-ethoxyresorufin O-deethylase (EROD) activity in the hepati
c microsomes (p <.01). Immunoinhibition assays with monoclonal anti-cy
tochrome P-450 (CYP) 1A1/1A2 (1-7-1) showed that the monoclonal antibo
dy-inhibitable EROD activity in the hepatic microsomes was increased b
y 59% (p <.01) and 40% (p <.05), respectively, in the HNO3 vapor and O
-3 plus HNO3 vapor groups. Benzphetamine N-demethylase activity was no
t significantly affected by exposure to either O-3 or HNO3 vapor in th
e hepatic microsomes. However, in the lung O-3 exposure caused a 72% i
ncrease in benzphetamine N-demethylase activity (p <.01). whereas this
activity was decreased by 15% by HNO3 vapor exposure (p <.01). In the
animals exposed to a combination of O-3 and HNO3 vapor, there was an
85% increase of benzphetamine N-demethylase activity in the lung (p <.
01). Total metabolism of H-3-benzo[a]pyrene was significantly increase
d in the hepatic microsomes prepared from the animals exposed to O-3 (
p <.01), HNO3 vapor (p <.01), and O-3 plus HNO3 vapor (p <.05) groups
compared to the air-exposed controls. Exposure to O-3, HNO3 vapor, and
O-3 plus HNO3 vapor resulted in a 3- 5.4-; and 7.2-fold increase in t
he metabolism of H-3-benzo[a]pyrene in the pulmonary microsomes (p <.0
1), suggesting that O-3 and HNO3 vapor may exert an additive action on
the metabolism of H-3-benzo[a]pyrene in the lung.