Changes in rat lung microsomal lipids after p‐xylene: Relationship to inhibition of benzo[a]pyrene metabolism

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Abstract
The relationship between p‐xylene's effects on microsomal membranes, cytochrome P‐450, and benzofajpyrene (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.