Emel Arinc - Academia.edu (original) (raw)

Papers by Emel Arinc

Reconstitution of the Rabbit Pulmonary Microsomal Mixed-Function Oxidase System from Solubilized Components

Drug Metabolism and Disposition, Mar 1, 1975

Lung microsomal cytochrome P-450 was solubilized and purified 2-fold. NADPH-cytochrome c reductas... more Lung microsomal cytochrome P-450 was solubilized and purified 2-fold. NADPH-cytochrome c reductase (EC 1.6.2.3) was solubilized and purified 4-6 fold by three methods with use of sonication and detergent digestion followed by either DEAE-cellulose chromatography or ammonium sulfate fractionation. Benzphetamine N-demethylase and 7-ethoxycoumarin deethylase activities were reconstituted when NADPH-cytochrome c reductase and cytochrome P-450 fractions were combined. Reductase fractions prepared by sodium cholate digestion of microsomes were highly active in supporting the hydroxylation activity in the reconstituted systems, whereas those prepared with sodium deoxycholate were not. About twice as much NADPH-cytochrome c reductase was required for saturation of the 7-ethoxycoumarin deethylase activity as for saturation of the benzphetamine N-demethylase activity. A heat-stable lipid fraction was necessary for maximum hydroxylation activity. NADH did not support benzphetamine N-demethylation in the reconstituted system or increase the rate of reaction when added with NADPH.

Arinç, E., and Şen, A., Cytochrome P4501A1 associated enzyme activaties of fish as an indicator of pollution with special reference to İzmir Bay. pp. 247-457. In: Arinç, E., Schenkman, J. B., Hodgson, E. (editors), Molecular and Applied Aspects of Oxidative Drug Metabolizing Enzymes. NATO ASI Ser...

Arinç, E., Kocabıyık, S., and Su, E.: Induced CYP mRNA, protein and catalytic activity in the liver of feral fish, leaping mullet, Lisa saliens Comp arative Biochemistry and Physiology C. Pharmacology, Toxicology and Endocrinology, 128C (No.2) (February), 281-290, 2001

Pharmacogenetics of Thiopurine Methyltransferase in Treatment of Acute Lymphoblastic Leukemiawith 6-MERCAPTOPURINE in Turkish Children-Discordant Cases

Pediatric Blood & Cancer

Molecular aspects of oxidative drug metabolizing enzymes : their significance in environmental toxicology, chemical carcinogenesis, and health

Toxicol Lett, 1996

Hyperthermia causes several congenital abnormalities in a number of domestic and laboratory speci... more Hyperthermia causes several congenital abnormalities in a number of domestic and laboratory species of mammals, including defects on the central nervous system [1]. The purpose of this study was to investigate the effects of prenatal hyperthermia exposure on developmental and behavioral repertoire of the offspring, through 12 weeks of age. Pregnant Wistar rats were exposed to 37 (control), 40, 41 or 42°C, for 15 minutes once dally, by partial immersion in a water bath, from gestational day 15 to 21. Dams were allowed to deliver normally. Litters were culled to eight pups at birth and fostered to normal lactating dams. No maternal or reproductive toxicity was detected. Surface righting, negative geotaxis, wire hanging maneuver and sexual behavior revealed no differences between hyperthermia exposed offspring and control groups. However, pre-weaning body weights were decreased in both, females and males. Physical landmarks such as pinna unfolding, tooth eruption and eye opening, were delayed in animals of both sexes. Clift avoidance and auditory startle developed also latter. Frequency and duration of entrances in an hole-board exploration test were significantly decreased. These results are consistent with the suggestion that hyperthermia is a potential behavioral teratogen.

J Mol Catal B Enzym, 2010

Inhibitors of some cytochrome P450s (CYPs) are used to design target-specific drugs. CYPs belongi... more Inhibitors of some cytochrome P450s (CYPs) are used to design target-specific drugs. CYPs belonging to families 1–4 play important roles in drug metabolism and therapeutics. Some isozymes of CYPs also activate pro-carcinogens into their carcinogenic forms. Approximately 40–50% human CYP-dependent drug metabolism is carried out by polymorphic CYPs resulting in therapeutic failure and adverse reactions. Phenotyping of CYPs involved in the metabolism of a drug is important to understand the potential of clinical interactions and to predict the possible individual variations due to genetic polymorphisms of certain CYPs.

Comp Biochem Physiol C Pharmacol Toxicol Endocrinol, 1998

CITATIONS 31 READS 15 2 authors: Some of the authors of this publication are also working on thes... more CITATIONS 31 READS 15 2 authors: Some of the authors of this publication are also working on these related projects: Effect and mechanism of the novel natural compound on the animal model of multiple sclerosis View project Alaattin SEN

$Research paper thumbnail of Different influences of two fractions of lung cytochrome b5 on reconstituted lung benzphetamine N-demethylase system$

Different influences of two fractions of lung cytochrome b5 on reconstituted lung benzphetamine N-demethylase system

The International Journal of Biochemistry Cell Biology, Nov 1, 1995

Chromatography of lung microsomal cytochrome b5 obtained from DEAE-cellulose columns, yielded two... more Chromatography of lung microsomal cytochrome b5 obtained from DEAE-cellulose columns, yielded two distinct cytochrome b5 fractions. These cytochrome b5 fractions were further purified by Sephadex G-100 gel filtration chromatography. The specific cytochrome b5 content of fraction 1 and fraction 2 was found to be 16.5 and 16.4 nmol/mg protein respectively. Both fractions were free of cytochrome P-450, NADPH-cytochrome P-450 reductase and NADH-cytochrome b5 reductase activities. The effects of lung cytochrome b5 (fraction 1 and fraction 2) and liver cytochrome b5 on benzphetamine N-demethylase activity were examined. Four different reconstitution systems were used. Lung cytochrome b5 fraction 2 and liver cytochrome b5 stimulated N-demethylase activity in all four systems when b5:P-450 molar ratio was low, i.e. 0.25 or 0.5. Both cytochrome b5 samples inhibited N-demethylase activity when b5:P-450 ratio exceeded 1:1 molar ratio. In contrast lung cytochrome b5 fraction 1 stimulated N-demethylase activity in all four systems. Maximal enhancement of the activity was obtained when b5:P-450 ratio was 0.5. The greatest increase in N-demethylation activity was observed in the reconstitution system with the lowest concentration of cytochrome P-450 reductase, conditions which most closely resemble intact microsomes.

Inhibitory effects of in vivo benzene treatment of cytochrome P450 and 7-ethoxyresorufin O-deethylase activities of gilthead seabream liver microsomes

Journal of basic and clinical physiology and pharmacology

A Comparison of the in vitro DNA-Damaging Potential of the Two Anticancer Drugs Idarubicin and Mitomycin C in the Presence of NADPH-Cytochrome P450 Reductase

Quinone-containing anticancer drugs are generally designed as prodrugs and these prodrugs are red... more Quinone-containing anticancer drugs are generally designed as prodrugs and these prodrugs are reductively activated into their radical intermediates in the cell by NADPH:cytochrome P450 reductase (E.C. 1.6.2.4) and also by a number of other reductive enzymes. Idarubicin and mitomycin c are among the most important bioreductive antitumor agents. In this study, we used purified sheep lung cytochrome P450 reductase to investigate whether differences exist in the activation of two drugs, idarubicin and mitomycin c, to generate strand breaks in DNA. The ability of drugs to induce DNA scission following activation by P450 reductase was determined by using cell-free agarose gel electrophoresis method. The extent of DNA strand breaks was found to increase with increasing either drug (1-400 µM), or enzyme concentration (0-1µg) as well as increasing incubation time upto 90 minutes. Control experiments where either the drug, enzyme or the cofactor omitted showed little or no evidence of DNA sc...

The Role of SULT1A1 and EPHX1 Polymorphisms as RISK Modifiers in Childhood Acute Lymphoblastic Leukemia in Turkish Population: A Case-Control Study

In recent years, epidemiological studies suggest that environmental chemicals bioactivated by cer... more In recent years, epidemiological studies suggest that environmental chemicals bioactivated by certain DMEs may play an important role in the etiology of development of childhood acute lymphoblastic leukemia (ALL). Epoxide hydrolase (EPHX1) and Sulfotransferase 1A1 (SULT1A) are susceptible DMEs in this respect, since they play a dual role in the detoxification and activation of a broad spectrum of environmental and tobacco derived carcinogens like benzene and polyaromatic hydrocarbons. Both of these enzymes have several SNPs, one of them is a histidine to arginine substitution in exon 4 (His139Arg) of the EPHX1 gene increases in vitro enzyme activity by 25%. In case of SULT1A1 gene, arginine to histidine substitution (Arg213His-SULT1A1*2) significantly reduces enzyme activity and thermostability. These two polymorphisms have been shown to modify risk of various chemically-induced cancer types like lung, gastric and bladder cancers. However, as far as we know, there is no study on the...

Tissue Dependent Expression of NADPH-Cytochrome P450 Reductase in Sheep

NADPH-cytochrome P450 reductase (E.C. 1.6.2.4) is an integral membrane flavoprotein present in th... more NADPH-cytochrome P450 reductase (E.C. 1.6.2.4) is an integral membrane flavoprotein present in the endoplasmic reticulum of a variety of tissues and is an essential component of the microsomal cytochrome P450 monooxygenase system. Up to now, cytochrome P450 monooxygenase system responsible for the metabolism of xenobiotics has been extensively studied in laboratory animals such as the rat and subsequently in humans. On the other hand, the detailed study of the components of this system in domestic, food-producing animals has received relatively very little attention. For this purpose, in this study we determined the expression of cytochrome P450 reductase in several tissues of sheep. NADPH-cytochrome P450 reductase of sheep lung microsomes was purified to apparent homogeneity from the detergent-solubilized microsomes by the refinement of methods previously used in our laboratory. The purified lung enzyme produced a single band on SDS-PAGE. To generate antibodies purified reductase e...

Bioactivation of Mitomycin C Responsible for Formation of "ROS" and DNA Scission by Lung Cytochrome P450 Reductase

Bioreductive anticancer prodrugs are a class of chemical agents that have received considerable i... more Bioreductive anticancer prodrugs are a class of chemical agents that have received considerable interest as anticancer drugs. Mitomycin c is the most widely used bioreductive antitumor agent. It has been used clinically for the treatment of the several different types of cancer including stomach, pancreas, colon, breast, lung and oesophagus. In this study, NADPH-cytochrome P450 reductase purified from sheep lung microsomes in our laboratory was used to determine the ability of mitomycin c to induce single strand breaks in pBR322 plasmid DNA following its reductive activation in the presence of cofactor NADPH. A cell-free agarose gel electrophoresis method was employed to determine the effects of varying concentrations of cytochrome P450 reductase, mitomycin c and incubation time on DNA damage. When only drug and DNA were incubated together, no scission of DNA was observed. Addition of reductase was necessary to accomplish DNA breaks. The extend of single-strand breaks in DNA was fou...

Tissue- and species-dependent expression of sheep lung microsomal cytochrome P4502B(LgM2)

Biochemistry and molecular biology international

Expression of sheep lung microsomal cytochrome P4502B(LgM2) isozyme was determined in lung and li... more Expression of sheep lung microsomal cytochrome P4502B(LgM2) isozyme was determined in lung and liver preparations from rabbits, rats, sheep, cows and humans. Several tissues of sheep such as lung, liver, adrenal, kidney, ovary, intestine, muscle, spleen, pancreas and brain were also examined. Tissue homogenates were analyzed by Western-blotting with an antibody raised against purified sheep lung P4502B(LgM2) isozyme in rabbits. This isozyme was detected in lung samples from every species examined. Homologues of cytochrome P4502B(LgM2) were expressed in livers of sheep and rabbits but not in those of humans and cows. Although homologous forms of P4502B(LgM2) were not expressed in sheep brain, ovary, pancreas, spleen and muscle tissues, they were expressed in sheep adrenal, intestine and kidney.

Comparative Biochemistry and Physiology Part C: Comparative Pharmacology, 1993

Involvement of Rabbit Liver Cytochrome P4502B4 in the Bioreduction of Idarubicin in Reconstituted Systems Containing Highly Purified P450 Reductase and P4502B4

Idarubicin is a second-generation anthracycline anticancer drug which is clinically effective aga... more Idarubicin is a second-generation anthracycline anticancer drug which is clinically effective against breast cancer and some hematological malignancies including acute myelogenous leukemia, multiple myeloma and non-Hodgkin’s lymphoma. Among the mechanisms proposed for the antitumor effects of anthracyclines, free radical generation via bioreductive activation and subsequent redox cycling under aerobic conditions is considered as having an important contributing role on the effectiveness of these chemotherapy agents. Free radical generation by anthracyclines involves their bioreductive activation by cellular oxidoreductases. The main objective of the present study was to investigate the possible role of cytochrome P450 in the bioreduction of idarubicin using reconstituted systems of purified rabbit liver cytochrome P4502B4 and either purified rabbit liver or beef liver cytochrome P450 reductase. In this study, all the experiments were also repeated under the same reaction conditions ...

Modulatory Effects of Quercetin, Quercitrin, Rutin, (-)-Epicatechin, (+)-Catechin, (+)-Taxifolin, Luteolin and Chrysin on Cytochrome b5 Reduction by NADH-Cytochrome b5 Reductase