Biomaterial Database

Effects of indomethacin and arachidonic acid on sister chromatid exchange induction by styrene and styrene-7,8-oxide. 1995

S H Lee, and H Norppa

Department of Preventive Medicine, Catholic University Medical College, Seoul, South Korea.

Styrene is converted into styrene-7,8-oxide in human lymphocyte cultures, in a reaction probably mediated by oxyhemoglobin. As a consequence, styrene induces sister-chromatid exchanges (SCEs) in whole-blood lymphocyte cultures without exogenous metabolic activation systems. Another metabolic pathway that could be involved in the metabolism of styrene is cooxidation by prostaglandin-endoperoxide synthase (PES). To study the role of PES in the metabolism of styrene, human whole-blood lymphocyte cultures were treated for the entire culture time of 72 h with styrene (0.5 and 1 mM) or styrene-7,8-oxide (50 and 100 microM), in the presence and absence of 75 or 150 microM indomethacin (an inhibitor of PES) and arachidonic acid (substrate of PES). Indomethacin potentiated SCE induction by both styrene and styrene-7,8-oxide; a slight but statistically significant enhancement (16-32%; p < 0.05-0p < 0.001) was observed in all treatments with styrene and at 150 microM indomethacin in the case of styrene-7,8-oxide. At 150 microM, arachidonic acid induced a 15-20% suppression (p < 0.01) in SCE induction by both styrene (1 mM only) and styrene-7,8-oxide (100 microM only). Indomethacin or arachidonic acid did not alone influence the frequency of SCEs. The results suggest that PES acts as an inactivation route for styrene and styrene-7,8-oxide in human whole-blood lymphocyte cultures, possibly through PES-mediated binding to glutathione.

UI	MeSH Term	Description	Entries
D007213	Indomethacin	A non-steroidal anti-inflammatory agent (NSAID) that inhibits CYCLOOXYGENASE, which is necessary for the formation of PROSTAGLANDINS and other AUTACOIDS. It also inhibits the motility of POLYMORPHONUCLEAR LEUKOCYTES.	Amuno,Indocid,Indocin,Indomet 140,Indometacin,Indomethacin Hydrochloride,Metindol,Osmosin
D008214	Lymphocytes	White blood cells formed in the body's lymphoid tissue. The nucleus is round or ovoid with coarse, irregularly clumped chromatin while the cytoplasm is typically pale blue with azurophilic (if any) granules. Most lymphocytes can be classified as either T or B (with subpopulations of each), or NATURAL KILLER CELLS.	Lymphoid Cells,Cell, Lymphoid,Cells, Lymphoid,Lymphocyte,Lymphoid Cell
D008297	Male		Males
D009153	Mutagens	Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes.	Clastogen,Clastogens,Genotoxin,Genotoxins,Mutagen
D010084	Oxidation-Reduction	A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471).	Redox,Oxidation Reduction
D002478	Cells, Cultured	Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.	Cultured Cells,Cell, Cultured,Cultured Cell
D004305	Dose-Response Relationship, Drug	The relationship between the dose of an administered drug and the response of the organism to the drug.	Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004852	Epoxy Compounds	Organic compounds that include a cyclic ether with three ring atoms in their structure. They are commonly used as precursors for POLYMERS such as EPOXY RESINS.	Epoxide,Epoxides,Epoxy Compound,Oxiranes,Compound, Epoxy,Compounds, Epoxy
D005978	Glutathione	A tripeptide with many roles in cells. It conjugates to drugs to make them more soluble for excretion, is a cofactor for some enzymes, is involved in protein disulfide bond rearrangement and reduces peroxides.	Reduced Glutathione,gamma-L-Glu-L-Cys-Gly,gamma-L-Glutamyl-L-Cysteinylglycine,Glutathione, Reduced,gamma L Glu L Cys Gly,gamma L Glutamyl L Cysteinylglycine
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man