1. m-Xylene (1 g/kg, i.p., 1 h) increased formation of benzo(a)pyrene (BP) mutagenic bay region diols, BP-7,8-diol (66%) and BP-9,10-diol (56%) by rat pulmonary microsomal preparations, while formation of individual BP phenols and quinones was unaltered. 2. m-Xylene administration produced a decrease in cytochrome P450IIB1 activity as measured by pentoxy- and benzyloxy-resorufin O-dealkylation (PROD, BROD), while cytochrome P450IA1 activity, expressed as ethoxyresorufin O-dealkylation (EROD), was unaltered. 3. Pulmonary microsomal epoxide hydrolase activity was also unaltered by m-xylene. 4. In summary, m-xylene alters the relative contribution of P-450 isozymes to BP metabolism resulting in inhibition of BP detoxication and increased production of toxic metabolites.
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.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.