Abstract
Rats carrying minipumps filled with 5-bromo-2′deoxyuridine were exposed to ozone, NO2, or a mixture of the two gases using four different protocols: (A) ozone 0.2 ppm, NO2 3.6 ppm, or their mixture for 24 hr a day; (B) ozone 0.4 ppm, NO2 7.2 ppm, or their mixture for 12 hr per night; (C) ozone 0.6 ppm, NO2 10.8 ppm, or their mixture for 8 hr per night; and (D) ozone 0.8 ppm, NO2 14.4 ppm, or their mixture for 6 hr per night. After three consecutive daily exposures, the animals were returned to filtered air and killed 7 days after implantation of the mini-pump. Alveolar labeling indices were comparable to control values except in the group of animals exposed for 6 hr nightly to a combination of 0.8 ppm of ozone and 14.4 ppm of NO2. Labeling indices in the peripheral airways were the most sensitive exposure index since they were significantly increased over control values in all animals exposed to ozone, NO2, or a mixture of the two gases, regardless of concentration or exposure duration. Labeling indices increased with elevated dose rate, i.e., concentration of the gases in the inspired air. The response to the combined gases was greater than the calculated sum of the responses to the two individual gases for the three higher dose rates in the large airways and for the highest dose rate in the peripheral airways. The results led to the following conclusions: (1) By the criterion of analysis of cell kinetics in rat large and peripheral airways, neither ozone, NO2, nor their mixture follows Haber′s law (c × t = k) over the concentration ranges studied; and (2) at the higher dose rates studied, there is a more than additive (synergistic) airway response to the combination of ozone and NO2.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 186-192 |
| Number of pages | 7 |
| Journal | Toxicology and Applied Pharmacology |
| Volume | 121 |
| Issue number | 2 |
| DOIs | |
| State | Published - Aug 1993 |
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ASJC Scopus subject areas
- Toxicology
- Pharmacology
Cite this
Alveolar and Airway Cell Kinetics in the Lungs of Rats Exposed to Nitrogen Dioxide, Ozone, and a Combination of the Two Gases. / Rajini, P.; Gelzleichter, T. R.; Last, Jerold A; Witschi, H.
In: Toxicology and Applied Pharmacology, Vol. 121, No. 2, 08.1993, p. 186-192.Research output: Contribution to journal › Article
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TY - JOUR
T1 - Alveolar and Airway Cell Kinetics in the Lungs of Rats Exposed to Nitrogen Dioxide, Ozone, and a Combination of the Two Gases
AU - Rajini, P.
AU - Gelzleichter, T. R.
AU - Last, Jerold A
AU - Witschi, H.
PY - 1993/8
Y1 - 1993/8
N2 - Rats carrying minipumps filled with 5-bromo-2′deoxyuridine were exposed to ozone, NO2, or a mixture of the two gases using four different protocols: (A) ozone 0.2 ppm, NO2 3.6 ppm, or their mixture for 24 hr a day; (B) ozone 0.4 ppm, NO2 7.2 ppm, or their mixture for 12 hr per night; (C) ozone 0.6 ppm, NO2 10.8 ppm, or their mixture for 8 hr per night; and (D) ozone 0.8 ppm, NO2 14.4 ppm, or their mixture for 6 hr per night. After three consecutive daily exposures, the animals were returned to filtered air and killed 7 days after implantation of the mini-pump. Alveolar labeling indices were comparable to control values except in the group of animals exposed for 6 hr nightly to a combination of 0.8 ppm of ozone and 14.4 ppm of NO2. Labeling indices in the peripheral airways were the most sensitive exposure index since they were significantly increased over control values in all animals exposed to ozone, NO2, or a mixture of the two gases, regardless of concentration or exposure duration. Labeling indices increased with elevated dose rate, i.e., concentration of the gases in the inspired air. The response to the combined gases was greater than the calculated sum of the responses to the two individual gases for the three higher dose rates in the large airways and for the highest dose rate in the peripheral airways. The results led to the following conclusions: (1) By the criterion of analysis of cell kinetics in rat large and peripheral airways, neither ozone, NO2, nor their mixture follows Haber′s law (c × t = k) over the concentration ranges studied; and (2) at the higher dose rates studied, there is a more than additive (synergistic) airway response to the combination of ozone and NO2.
AB - Rats carrying minipumps filled with 5-bromo-2′deoxyuridine were exposed to ozone, NO2, or a mixture of the two gases using four different protocols: (A) ozone 0.2 ppm, NO2 3.6 ppm, or their mixture for 24 hr a day; (B) ozone 0.4 ppm, NO2 7.2 ppm, or their mixture for 12 hr per night; (C) ozone 0.6 ppm, NO2 10.8 ppm, or their mixture for 8 hr per night; and (D) ozone 0.8 ppm, NO2 14.4 ppm, or their mixture for 6 hr per night. After three consecutive daily exposures, the animals were returned to filtered air and killed 7 days after implantation of the mini-pump. Alveolar labeling indices were comparable to control values except in the group of animals exposed for 6 hr nightly to a combination of 0.8 ppm of ozone and 14.4 ppm of NO2. Labeling indices in the peripheral airways were the most sensitive exposure index since they were significantly increased over control values in all animals exposed to ozone, NO2, or a mixture of the two gases, regardless of concentration or exposure duration. Labeling indices increased with elevated dose rate, i.e., concentration of the gases in the inspired air. The response to the combined gases was greater than the calculated sum of the responses to the two individual gases for the three higher dose rates in the large airways and for the highest dose rate in the peripheral airways. The results led to the following conclusions: (1) By the criterion of analysis of cell kinetics in rat large and peripheral airways, neither ozone, NO2, nor their mixture follows Haber′s law (c × t = k) over the concentration ranges studied; and (2) at the higher dose rates studied, there is a more than additive (synergistic) airway response to the combination of ozone and NO2.
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U2 - 10.1006/taap.1993.1144
DO - 10.1006/taap.1993.1144
M3 - Article
VL - 121
SP - 186
EP - 192
JO - Toxicology and Applied Pharmacology
JF - Toxicology and Applied Pharmacology
SN - 0041-008X
IS - 2
ER -