Metabolism of 1-[14C]nitropyrene in respiratory tract tissue of rats exposed to diesel exhaust.
The purpose of this study was to determine how prior exposure of rats to graded concentrations of diesel exhaust would affect respiratory tract tissue metabolism of 1-nitropyrene (NP), a known constituent of diesel exhaust. Rats were exposed (whole body) 7 hr/day, 5 days/week for 4 weeks to clean air (controls) or to diluted diesel exhaust containing concentrations of 350, 3300, and 7400 micrograms particles/m3. After exposures, nasal tissue and lungs from rats were tested for their ability to metabolize NP. Rat nasal tissue was incubated for 10 min with 20 microM 1-[14C]NP. Isolated perfused rat lungs were perfused for 90 min with 25 microM 1-[14C]NP. NP metabolites formed in rat nasal tissue and the isolated perfused rat lung were separated by high-pressure liquid chromatography. Exposure of rats to 7400 micrograms particles/m3 for 4 weeks resulted in significant increases (twofold) in rates of NP metabolism in both nasal tissue (440 pmol/mg protein/min) and the isolated perfused rat lung (112 nmol/g lung). Exposure of rats to lower concentrations of diesel exhaust did not increase the rates of NP metabolism in either rat nasal tissue or perfused rat lungs. In all cases, the major metabolites of NP formed in nasal tissue and perfused lungs were 3-, 6-, and 8-hydroxy-1-nitropyrene and 4,5-dihydro-4,5-dihydroxy-1-nitropyrene. A fourfold increase was observed in the amounts of 14C covalently bound in lungs from rats exposed to 7400 micrograms particles/m3. The results from this study indicate that exposure to diesel exhaust particles significantly alters metabolism and subsequent covalent binding of NP.
J A
JA
Bond
J L
JL
Mauderly
R F
RF
Henderson
R O
RO
McClellan
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D009297:Nasal Mucosa / Q000378:metabolism; D009666:Nose / Q000187:drug effects; D011721:Pyrenes / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D012137:Respiratory System / Q000187:drug effects* / Q000378:metabolism; D001335:Vehicle Emissions / Q000009:adverse effects*
D011721:Pyrenes; D001335:Vehicle Emissions; C032668:1-nitropyrene