Endotoxin or cytokines attenuate ozone-induced DNA synthesis in rat nasal transitional epithelium

Journal Article · Mon Jun 01 04:00:00 EDT 1992 · Toxicology and Applied Pharmacology; (United States)

DOI:https://doi.org/10.1016/0041-008X(92)90067-3· OSTI ID:7206327

Hotchkiss, J A; Harkema, J R ^[1]

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1. Inhalation Toxicology Research Institute, Albuquerque, NM (United States)

Pretreatment of rats with endotoxin (E), a potent inducer of tumor necrosis factor alpha (TNF), and interleukin 1 beta (IL 1), or a combination of TNF and IL1, has been shown to increase levels of lung antioxidant enzymes and protect against pulmonary toxicity associated with hyperoxia. Inhalation of ozone (O3) induces cell injury, followed by increased DNA synthesis, cell proliferation, and secretory cell metaplasia in rat nasal transitional epithelium (NTE). This study was designed to test the effects of E, TNF, and IL1 pretreatment on acute O3-induced NTE cell injury as measured by changes in NTE cell DNA synthesis. Rats were exposed to either 0.8 ppm O3 or air for 6 hr in whole-body inhalation chambers. Immediately before exposure, rats in each group were injected intraperitoneally (ip) with either saline alone or saline containing E, TNF, IL1, or both TNF and IL1. Eighteen hours postexposure, rats were injected ip with bromodeoxyuridine to label cells undergoing DNA synthesis and were euthanized 2 hr later. NTE was processed for light microscopy and immunochemically stained to identify cells that had incorporated BrdU into nuclear DNA. The number of BrdU-labeled NTE nuclei per millimeter of basal lamina was quantitated. There were no significant differences in the number of BrdU-labeled NTE nuclei in air-exposed rats that were injected with E, TNF, IL1, or TNF/IL1 compared with those in saline-injected, air-exposed controls. Rats that were injected with saline and exposed to O3 had approximately 10 times the number of BrdU-labeled NTE nuclei than saline-injected, air-exposed control rats. O3 exposure also induced a significant increase in labeled nuclei in rats that were pretreated with TNF alone. In contrast, pretreatment with E, IL1, or TNF/IL1 attenuated the O3-induced increase in NTE DNA synthesis.

• OSTI ID: 7206327
• Journal Information: Toxicology and Applied Pharmacology; (United States), Journal Name: Toxicology and Applied Pharmacology; (United States) Vol. 114:2; ISSN TXAPA; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

560300* -- Chemicals Metabolism & Toxicology
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL TISSUES
ANIMALS
ANTIGENS
BIOLOGICAL EFFECTS
BODY
BODY AREAS
CELL PROLIFERATION
DNA REPLICATION
ENDOTOXINS
EPITHELIUM
EXPOSURE CHAMBERS
FACE
GROWTH FACTORS
HAZARDOUS MATERIALS
HEAD
INHALATION
INTAKE
LUNGS
LYMPHOKINES
MAMMALS
MATERIALS
MITOGENS
NECROSIS
NOSE
NUCLEIC ACID REPLICATION
ORGANIC COMPOUNDS
ORGANS
OZONE
PATHOLOGICAL CHANGES
PROTEINS
RATS
RESPIRATORY SYSTEM
RODENTS
TISSUES
TOXIC MATERIALS
TOXICITY
TOXINS
VERTEBRATES