The influence of inhaled formaldehyde on rat lung cytochrome P450.
The effect of formaldehyde (HCHO) inhalation on total cytochrome P450 in the lungs of Sprague-Dawley rats was assessed after single and repeated exposures to 0, 0.5, 3, and 15 ppm HCHO. Whole-body exposures were conducted in dynamic, monitored exposure systems for 6 hr/day, 5 days/week, for periods of exposure of 1 day, 4 days, 12 weeks, or 24 weeks. Lung microsomal fractions were prepared and total protein and cytochrome P450 were measured 18 hr after the end of exposure at each time point. Two separate sets of exposure studies were conducted, thus duplicating all measurements for each dose group and at each time point. There were no detectable levels of total lung P450 in any of the rats that received a single 6-hr exposure to all three HCHO doses, while control lung P450 levels were similar to that found for 4-day and 12-week control rats. After 4 days of repeated exposures, however, there was a highly significant, reproducible, and dose-dependent increase in lung P450 levels relative to controls, with the 0.5, 3, and 15 ppm groups demonstrating 387, 1026, and 1123% of control values, respectively. Lung P450 levels remained elevated at all HCHO concentrations through 12 and 24 weeks of exposure, although the percentage difference between exposed and control rats continually dropped throughout the course of long-term repeated exposures. While HCHO-exposed rats did have decreased total body weight relative to controls, lung microsomal protein and lung weight of nearly all of the HCHO-exposed rats was not significantly different from the controls. The initial inactivation of lung P450 after a single HCHO exposure is apparently a transient phenomenon, with dose-dependent induction of the total P450 levels in the lung as the pattern of response to repeated exposures to inhaled HCHO.
Dallas
C E
CE
Department of Pharmacology and Toxicology, University of Georgia College of Pharmacy, Athens, 30602.
Badeaux
P
P
Theiss
J C
JC
Fairchild
E J
EJ
D000280:Administration, Inhalation; D000395:Air Pollutants, Occupational / Q000009:adverse effects; D000818:Animals; D002274:Carcinogens, Environmental / Q000009:adverse effects; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005557:Formaldehyde / Q000008:administration & dosage / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D000395:Air Pollutants, Occupational; D002274:Carcinogens, Environmental; D005557:Formaldehyde; D003577:Cytochrome P-450 Enzyme System