The extent and persistence of binding to respiratory mucosal DNA by inhaled tritiated propylene oxide.
In order to investigate some of the mechanisms underlying the carcinogenicity of inhaled propylene oxide (PO), the deposition and persistence of inhaled tritiated PO in the DNA of the nasal cavities, tracheae and lungs of rats were investigated. The results of dose/response exposure protocols revealed clear gradients for binding throughout the respiratory mucosa; the highest levels of binding were in the nasal mucosa and the lowest were in the lungs. Gradients became steeper as exposure concentrations were lowered. The persistence studies revealed that bound tritium declined in nasal mucosal DNA with apparent bi-exponential kinetics while clearance from the tracheal and pulmonary DNA was much slower and occurred with apparent mono-exponential kinetics. Consequently, although the initial levels of binding of inhaled PO are lower in the trachea and lungs than in the nasal cavity, the slow clearance of PO from the DNA in these organs could increase the chances of a mutational event.
Snyder
C A
CA
New York University Medical Center, Nelson Institute of Environmental Medicine, Tuxedo 10987.
Solomon
J J
JJ
D000280:Administration, Inhalation; D000818:Animals; D004247:DNA / Q000378:metabolism*; D004852:Epoxy Compounds / Q000008:administration & dosage / Q000378:metabolism* / Q000493:pharmacokinetics; D007700:Kinetics; D008168:Lung / Q000378:metabolism*; D008297:Male; D009092:Mucous Membrane / Q000378:metabolism; D009297:Nasal Mucosa / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D014132:Trachea / Q000378:metabolism*; D014316:Tritium
D004852:Epoxy Compounds; D014316:Tritium; D004247:DNA; C009068:propylene oxide