Changes in rat lung microsomal lipids after p-xylene: relationship to inhibition of benzo[a]pyrene metabolism.
The relationship between p-xylene's effects on microsomal membranes, cytochrome P-450, and benzo[a]pyrene (BaP) metabolism was studied. p-Xylene (1 g/kg, ip, 1 h) inhibited 3-hydroxy BaP (3-OH) formation and decreased arylhydrocarbon hydroxylase (AHH) activity approximately 40% in rat lung microsomes. BaP dihydrodiol and quinone formation were unchanged by p-xylene administration. Cytochrome P-450 was below the limit of detection in lung microsomes from p-xylene-treated rats. Total phospholipid (PL) and phosphatidylcholine (PC) in microsomal membranes were decreased 28% and 17%, respectively. Cholesterol (CL), phosphatidylethanolamine (PE), phosphatidylserine (PS), phosphatidylinositol (PI), and sphingomyelin (SM) were unchanged. The net activity of enzymes involved in the synthesis of PC, phosphatidylethanolamine-N-methyltransferase I and II (PMT I and PMT II), was slightly elevated by p-xylene. PL/CL and PC/PE ratios, indicators of membrane fluidity, were decreased 34% and 13%, respectively, in microsomes from p-xylene-treated rats. Analysis of fluidity by fluorescence polarization showed that the actual fluidity of treated microsomes was slightly decreased (5%) as compared to controls. The decrease in P-450, PL, and PC is considered to contribute to the inhibition of BaP metabolism.
Roberts
A E
AE
Toxicology Program, Northeastern University, Boston, Massachusetts.
LeBel
C P
CP
Stickney
J A
JA
Silverman
D
D
Brown
D R
DR
Schatz
R A
RA
D000818:Animals; D001564:Benzo(a)pyrene / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis; D007425:Intracellular Membranes / Q000032:analysis* / Q000187:drug effects; D008168:Lung / Q000032:analysis* / Q000187:drug effects; D008297:Male; D008861:Microsomes / Q000032:analysis*; D010743:Phospholipids / Q000032:analysis; D051381:Rats; D011919:Rats, Inbred Strains; D014992:Xylenes / Q000494:pharmacology*
D010743:Phospholipids; D014992:Xylenes; D001564:Benzo(a)pyrene; C031286:4-xylene; D003577:Cytochrome P-450 Enzyme System