Effects of ozone inhalation on polyamine metabolism and tritiated thymidine incorporation into DNA of rat lungs
- Univ. of California, Los Angeles (USA)
We examined the effects of low-level ozone (O3) inhalation on polyamine metabolism and tritiated thymidine (3H-TdR) incorporation into DNA in rat lungs. We have also compared the activities of ornithine decarboxylase (ODC), the rate-limiting enzyme of polyamine biosynthesis, and glucose-6-phosphate dehydrogenase (G6PD), the key enzyme of the pentose phosphate cycle and a typical marker of oxidant injury, to assess whether ODC can serve as a sensitive marker of O3 effects on the lung. We exposed 90-day-old male specific-pathogen-free Sprague-Dawley rats to either 0.45 +/- 0.05 ppm (882 +/- 98 micrograms/m3) O3 or filtered room air continuously for 3 days. After exposure, the rats were terminated and the lungs examined for enzyme activities, polyamine contents, DNA content, and 3H-TdR incorporation. We found that in exposed rats, the enzyme activities were significantly increased (p less than 0.05) relative to air controls. G6PD, 25%, ODC, 147%, and S-adenosylmethionine decarboxylase (AdoMet DC), 86%. Polyamine contents were also affected by O3; putrescine increased 80%, p less than 0.05, spermidine did not change, and spermine decreased 23%, p less than 0.05. 3H-TdR incorporation into DNA was significantly elevated, 155%, p less than 0.001, after O3 exposure while total lung DNA content remained unchanged. The concomitant and large increase in ODC activity (reflecting polyamine metabolism) and DNA labeling (reflecting DNA synthesis and/or repair), indicates a strong correlation between the two and suggests that polyamine metabolism may play an important role in the accelerated cell proliferation associated with O3 injury. Moreover, the greater increase in lung ODC activity compared to other enzymes offers a sensitive marker of the lung response to inhaled O3.
- OSTI ID:
- 6982927
- Journal Information:
- Toxicology and Applied Pharmacology; (USA), Vol. 102:1; ISSN 0041-008X
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
59 BASIC BIOLOGICAL SCIENCES
AMINES
METABOLISM
DECARBOXYLASES
ENZYME ACTIVITY
LUNGS
SENSITIVITY
OXIDOREDUCTASES
OZONE
BIOLOGICAL EFFECTS
BIOLOGICAL MARKERS
DNA
DOSE-RESPONSE RELATIONSHIPS
EXPOSURE CHAMBERS
INHALATION
RATS
THYMIDINE
TRACER TECHNIQUES
TRITIUM COMPOUNDS
ANIMALS
AZINES
BODY
CARBON-CARBON LYASES
CARBOXY-LYASES
ENZYMES
HETEROCYCLIC COMPOUNDS
HYDROGEN COMPOUNDS
INTAKE
ISOTOPE APPLICATIONS
LYASES
MAMMALS
NUCLEIC ACIDS
NUCLEOSIDES
NUCLEOTIDES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PYRIMIDINES
RESPIRATORY SYSTEM
RIBOSIDES
RODENTS
VERTEBRATES
560300* - Chemicals Metabolism & Toxicology
550501 - Metabolism- Tracer Techniques