Pulmonary microsomal alterations following short-term low level inhalation of p-xylene in rats.
Rats exposed to 300 ppm para-xylene vapor for 1, 3 or 5 days, 6 h/day, exhibited alterations in pulmonary microsomal membrane structural and metabolic parameters. Following 1 day of exposure, conjugated diene levels were elevated while total phospholipid levels, P-450 content, benzyloxyresorufin O-dealkylase activity and 2-aminofluorene N-hydroxylase activity were decreased. Core and leaflet membrane fluidity, ethoxyresorufin O-deethylase activity and aryl hydrocarbon hydroxylase (AHH) activity were unchanged at this time. Altered parameters began to return to control values by day 3 of exposure except for 2-aminofluorene N-hydroxylase activity, which remained decreased throughout the time course, and core membrane fluidity which was increased following 3 days of exposure. After 5 days of exposure, all parameters returned to control levels with the exception of AHH activity which was increased 41% at this time. Extracellular surfactant levels were also decreased by 1 and 3 days of exposure but returned to control values after 5 days. Initial pulmonary alterations produced by low level p-xylene exposure may be mediated by a peroxidative process. The initial damage triggers an adaptive response in lung tissue which possibly involves enzyme induction and/or cell proliferation. The increase in AHH activity after 5 days of exposure could have important consequences on the metabolism of co-administered xenobiotics.
Silverman
D M
DM
Toxicology Program, Northeastern University, Boston, MA 02115.
Schatz
R A
RA
D000280:Administration, Inhalation; D000818:Animals; D002462:Cell Membrane / Q000187:drug effects; D008168:Lung / Q000187:drug effects*; D008297:Male; D008861:Microsomes / Q000187:drug effects* / Q000201:enzymology / Q000648:ultrastructure; D006899:Mixed Function Oxygenases / Q000187:drug effects / Q000378:metabolism; D011663:Pulmonary Surfactants / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D014992:Xylenes / Q000008:administration & dosage / Q000633:toxicity*
D011663:Pulmonary Surfactants; D014992:Xylenes; C031286:4-xylene; D006899:Mixed Function Oxygenases