SUBJECT INDEX Acidic phospholipids on protein kinase cAMP-dependent protein kinase C 351, 354, 359 (cAMP-PK) Acivicin of yeast 110-112 in combination with dipyridamole 46-48 mutant 113 inhibition of de novo purine phosphorylation of synthesis 54 glycogen synthase 105, 106 inhibition of de novo pyrimidine synapsin I 352, 359 synthesis 48 sites of 357 Acquired immunodeficiency syndrome Amylase (EC 3.2.1.1) gene induction by (AIDS) treatment with AZT 85, 86 insulin 188 Actin-tropomyosin interactions, troponin T regulatory sequences 190 regulation 264 Antibodies 6-Actin insulin negative regulatory brain specific, hydrophobization 426 sequence 190 polyclonal, against influenza virus Adenosine-3’ ,5'-cyclophosphate see cAMP hydrophobized, on virus withdrawal Adenylate cyclase (EC 4.6.1.1) control in from cell 425, 428 yeast 111, 112 on viral reproduction 421-423 Adenylate kinase (EC 2.7.4.3) phosphate antigenic determinant interaction site 176 specificity 422-424 Adipocyte differentiation assay 419 from 3T3 cells 197 effect of stearoylation 421-424 insulin on 201, 214, 217 production and modification 418, lipoprotein lipase activity 419 and 201-204, 217 polyclonal, against respiratory-synticial phenobarbital on 201-204, 214, 217 virus lipoprotein lipase and 197 on viral reproduction 421 stochastic model 214 assay 419 Adipose tissue, lipoprotein lipase effect of stearoylation 421 levels purification 418 during fasting 196, 207 Anticarcinogens, curcumin and related heparin on 209 dietary compounds 385-394 phenobarbital on 214 Antifolates in chemotherapy 13-24 synthesis in 195 Antiglucocorticoid 5-a-pregnane-3 ,20-dione ADP reductase inhibition by on tyrosine aminotransferase Amidox 77, 80 expression 250 Didox 77, 80 Antiglucocorticoid RU486 on Albumin gene induction by insulin 188 5-azacytidine induced tyrosine Alcohol dehydrogenase (EC 1.1.1.1) aminotransferase 253 ribose binding site 176 dexamethasone induced serine secondary structures 146, 152 dehydratase 252, 257 Allopurinol chemotherapy 57, 58, 437 dexamethasone induced tyrosine inhibition of xanthine aminotransferase 248, 252, 257 dehydrogenase 57, 58 glucocorticoid receptor 255-257 and decrease of uric acid 57 Antiinflammatory action of curcumin and and increase of plasma related compounds 390-392, 394 hypoxanthine 57, 58 Antimalarials, development of 439 with tiazofurin 57 Antisense oligonucleotides (oligos) see Amidox see 3,4-Dihydroxybenzamidoxime Oligonucleotides, antisense cAMP Apolipoprotein C-II second messenger role 351 binding to lipoprotein lipase 196 system of yeast 111, 112 requirement by lipoprotein lipase 195 465 466 SUBJECT INDEX Arachidonic acid Bovine adrenal P450 induced edema, inhibitors of 391, 392 coexpression with P450.,, 374-376 metabolism to hydroxyeicosatetraenoic in steroid metabolism 370-373 acids, inhibitors of 392 metabolism to prostaglandins, inhibitors of 393, 394 Ca2+ Aryl hydrocarbon hydroxylase (AHH) -dependent enzymes 351 induction by polycyclic hydrocarbons intracellular concentration on 307 neurotransmission 352 Aryl hydrocarbon (Ah) receptor role in glycogen synthase bending of DNA 311 phosphorylation 105, 113 implication in dioxin action 308 second messenger role 351 interaction with specific DNA Ca2+-dependent protease (CANP) insulin sequence 310 negative regulatory sequence 190 properties, by DNA crosslinking Ca?*+protein kinase see Protein kinase studies 311 Caffeic acid properties, comparison with steroid inhibition receptors 314 of lipoxygenase activity 392, 393 Aspartate production in various cells 237 of TPA-induced ODC activity 388, Atherosclerosis 389 low density lipoprotein receptors of TPA-induced tumor and 196 production 385-388 use of heparin in 198 on 5-Azacytidine arachidonic acid induced mouse-ear hepatic gene-specific regulation by 249 edema 391 induced hypomethylation of DNA 247 colon cancer induction 388 induction of serine dehydratase in cyclooxygenase activity 393, 394 suckling rats, effect of hormones 251 TPA-induced mouse-ear edema 390 induction of tyrosine aminotransferase in structure 386 suckling rats 247-257 Calmodulin (CaM) effect of adrenalectomy 252, 257 -dependent protein kinase see Protein effect of hormones 251 kinase time dependence 250, 251 regulation of PKC phosphorylation of with dexamethasone 251 synapsin I 354, 358, 359 on glucocorticoid receptor 253-256 Cancer on hepatic morphology in fetal rats cachexia, increased glutamine release 250 from muscles and 244 3'-Azido-3'-deoxythymidine (AZT) cells genetic changes in 329, 335 competitive inhibition of thymidine Candida elegans TPA-resistant mutant, kinase in cancer cells 49 nPKC gene 291 in conjunction with 5-FU 50, 52, 53 Carbodiimide reaction with protein in conjunction with MTX 50-53 kinases 176-178 inhibition of HIV replication 86 Carboplatin (cis-diamine-1,1- mechanism of 91, 94 cyclobutanedicarboxylate-platinum with FLT 90, 94 (II), Paraplatin) with PFA 88, 89, 94 bioavailability 35 inhibition of reverse transcriptase 86 in Ovarian tumor chemotherapy 31 mode of action 86, 87 on human ovarian tumor with PFA 88, 89 xenografts 37-39 mode of anti-retroviral action 47 Carboxypeptidase-A (CP-A, EC 3.4.17.1) structure 48, 87 activation of MTX-Ala 4 treatment of AIDS 85, 86 derivatization 5, 11 3'-Azido-3'-deoxythymidine triphosphate Carboxypeptidase-A/monoclonal conjugate (AZT-TP) inhibition of reverse antigen-binding activity 7, 8 transcriptase with cytotoxicity with MTX-Ala 8-10 FLT-TP 90, 91, 94 enzyme activity 7,8 PFA 88, 89, 94 preparation 5, 6 SUBJECT INDEX properties 7 6-MP 436, 437 purification 6, 7, 11 Pt coordination complexes 31-42 stability 8,9 sulfamethoxazole 439, 440 Carcinogenesis studies, designer sulfonamides 439 membranes in 376 trimethaprim 439, 440 Carcinogens in human diet 385 Chloramphenicol acetyltransferase (CAT) Cardiac muscle, lipoprotein lipase synthesis gene in 195 connection to GST-P gene 320 Casein gene induction by insulin 186, 188 PKCs on 297, 298 Casein kinase I (CK-I) Chlorogenic acid of yeast 110, 111 inhibition of phosphorylation of glycogen lipoxygenase activity 392, 393 synthase 105, 106 TPA-induced mouse-ear edema 390 phosphorylation sites 107-109 TPA-induced ODC activity 388, 389 Casein kinase II (CK-II) TPA-induced tumor of yeast 110, 111 promotion 385-388 phosphorylation of glycogen on synthase 105, 106 arachidonic acid-induced mouse-ear phosphorylation sites 107, 108 edema 390 Catecholamines in glycogen synthase colon cancer 388 control 109 cyclooxygenase activity 393, 394 CB 3717 see structure 386 N!0-Propargyl-5 ,8-dideazafolate Cholesterol CDP reductase inhibition by concentrations, heparin on 205 Amidox 77 metabolism, role of P450 369 Didox 77, 80 transport 195 MAIQ 80 Chromatin structure, dioxin on 312, 314 Cell Chromosome abnormalities in human division, role of branched pathways 231 neuroblastoma 329, 330 nucleus, inositol lipid turnover association with amplified MYCN 330, in 399-413 333 signalling double minutes (DMs) 330 anionic phospholipids in 411 homogeneously staining region key step in 399 (HSR) 330 Chemotherapy Cisplatin cis-diamminedichloroplatinum (II) antifolate 13-24 bioavailability 35 antiviral with limitations as anticancer drug 31 hydrophobized antibodies 426, 428 on human ovarian carcinoma hydrophobized antisense xenografts 37-39 oligonucleotides 428 resistance, Pt drugs which carboxypeptidase-A/monoclonal circumvent 31-42 antibody 3-11 -resistant combination ADJ/PC6 plasmacytoma 40 acivicin with dipyridamole 46-48 human ovarian carcinoma cell AZT with 5-FU 50, 53 lines 40, 41 AZT with MTX 50, 53 L1210 cell lines 39 on HIV 92, 94 Citrate synthase (EC 4.1.3.7) maximum on ribonucleotide reductase activities in various cells 238, 239, sub-units 79 241-243, 245 tiazofurin with allopurinol 57 Contractile protein isoform diversity 261, hydrophobization of antibodies and 262 antisense oligonucleotides 417-429 COS1 cells see Monkey kidney on de novo and salvage pathways 45-65 Coumarin 7-hydroxylase activity, P450 objectives of 46 mutation on 378, 379 use of monoclonal antibodies 3 Curcumin with inhibition of allopurinol 437 arachidonic acid-induced mouse-ear 468 SUBJECT INDEX edema 391 superfamily 365, 366 cyclooxygenase activity 393, 394 designated numbering 366 lipoxygenase activity 392, 393 Cytochrome P450IA1 TPA-induced mouse-ear edema 390 assay 307 TPA-induced ODC activity 388, 389 induction by dioxin 307-315 TPA-induced tumor mechanism of action 312, 313 promotion 385-388 tumor promotion 385-394 source of 386 Deoxyribonucleotide 5’triphosphates structure 386 Amidox on pools 77, 78 synthetic analogs assay 74 inhibition of TPA-induced mouse-ear Didox on pools 77, 78 edema 390 2-Desamino-2-methyl-5 ,8-dideazafolate inhibition of TPA-induced ODC analog of CB 3717 14 activity 389, 390 2-Desamino-2-methyl-N!°-propargyl-5, structures 388 8-dideazafolic acid (ICI 198583) Cyclooxygenase (EC 1.14.99.1) activity analog ICI D1694_ 15, 17 curcumin inhibition of 393, 394 cytoxicity and drug retention 23 CYPIAI gene hematological toxicity 24 encoding cytochrome P450IA1 307 inhibition of dihydrofolate regulation of 308 reductase 22 transcription, dioxin activation 307-309 polyglutamation on inhibition of enhancement elements 309, 310 thymidylate synthase 22, 24 in vitro 312 structure 22 mechanism of action 312, 313 hererocyclic ring modifications 16, 17 promoter 310 on folypolyglutamate synthetase Cytidine metabolism in L1210 cells substrate activity 20, 21 Amidox on 76, 80, 81 on growth inhibition 17, 18 Didox on 76, 80, 81 on MTX-resistant L1210 cells 19 Cytochrome b, on P450 activity 379, 380 on thymidylate synthesis 17 Cytochromes P450 inhibition of TS 14 activity with various substrates, polyglutamation 14, 15 cytochrome b; on 379, 380 Designer membranes, controlled enzyme cell types used for expression 377 composition 375 designer membranes 375, 376 in sequential metabolism studies 376 cDNAs of 366 Dexamethasone transfection of COS cells 367-369 binding to glucocorticoid expression receptor 253-256 as fusion protein with reductase 378, induction of DH in suckling rats 251 379 RU486 on 252 in COS cells 368-371 induction of TAT in suckling rats 248 17a-hydroxylation of progesterone RU486 on 248, 252, 257 and pregnenolone 368-370 time dependence 250, 251 in E. coli 376 with 5-azacytidine 251 generation of reactive metabolites 366 Diacylglycerol (DAG, tumor production or cell death 1 ,2-diacyl-Sn-glycerol) from 367 activation heterologous expression 365-381 of PKCs 287, 292, 356 co-transfection 379, 380 on nPKCe 292 fusion proteins 378, 379 on gene expression 296 ‘humanized’ yeast cells 380 in glycogen synthase mutagenesis 378, 379 phosphorylation 105 17a-hydroxylases from different second messenger role 351 species 372-374 Diacyl glycerol (DAG) kinase in nuclear primary function 365 fractions 404 simultaneous expression of two Didox see 3, 4-Dihydroxybenzohydroxamic P450s 374-376 acid SUBJECT INDEX Diferuloylmethane see Curcumin of [(2)gl gene 341 Dihydrofolate reductase (DHFR, EC Dog kidney (MDCK) cells 1.5.1.4) culture 418 antifolate target 13, 18 influenza virus infection 420-422 gene mutation on alternative Drosophila melanogaster splicing 279 embryo transformation by P-/(2)g/ inhibition by ICI D1694 and transposons 341, 345 derivatives 22 genetics of neoplasia 339 inhibitors 439, 440 1(2)gl gene trimethaprim interaction 441 codon usage 346, 347 2,3-Dihydro-1h-imidazo(1,2-b)pyrazole duplication of transcription initiation (IMPY) inhibition of ribonucleotide site 340-342, 348 reductase 79 mRNA decay 344-347 3,4-Dihydroxybenzamidoxime (Amidox) spatio-temporal expression 342-344, inhibition of ribonucleotide 348 reductase 76, 77, 80 translation initiation site 342 on protein kinase C genes 291 cytidine metabolism 76, 80, 81 tumor suppressor gene L1210 cell cycle distribution 78 expression 339-349 L1210 cell growth 74, 75, 79 L1210 HU-7 cell growth 74, 75, 79 Epidermal growth factor receptor structure 72 (EGFR) insulin negative regulatory 3,4-Dihydroxybenzohydroxamic acid sequence 190 (Didox) Escherichia coli P450s expression inhibition of ribonucleotide in 376-378 reductase 76, 77, 80 Evolution of phosphorylation control in on glycogen synthase 114 cytidine metabolism 76, 80, 81 L1210 cell cycle distribution 78 L1210 cell growth 74, 75, 79 Familial hypercholesterolemia, low density L1210 HU-7 cell growth 74, 75, 79 lipoprotein receptors and 196 properties 71 Fatty acid modification of structure 72 antisense oligonucleotides 420, 427 1,2-Dioleoyl-Sn-glycerol (DOG) on antiviral antibodies 418, 419, 421 phosphorylation of SI by PKC 356 Fatty acid synthetase (FAS, EC 2.3.1.85) Dipyridamole gene induction by insulin 186, 188 blocking of salvage precursors 48 Ferulic acid in combination with acivicin 46-48 inhibition of Dioxin see lipoxygenase activity 392, 393 2,3,7,8,-Tetrachlorodibenzo-p-dioxin TPA-induced ODC activity 388, 389 DNA TPA-induced tumor promotion -Ah receptor binding, dioxin 385-388 induction 310 on methylation protection 311, 314 arachidonic acid-induced mouse-ear bending by Ah receptor 311 edema 391 chromatin configuration and 312 cyclooxygenase activity 393, 394 electrophoresis and structural forestomach carcinogenesis in arrangement of amplified mice 388 MYCN 332, 333 TPA-induced mouse-ear edema 390 hypomethylation structure 386 5-azacytidine induction 247 3'-Fluoro-3’deoxythymidine (FLT) gene expression and 247 inhibition of cDNA HIV replication 86 cytochrome P450 with AZT 90, 94 for production of heterologous active reverse transcriptase 86 enzyme 366 mode of action 86, 87 transfection of COS cells 367, 368 structure 87 470 SUBJECT INDEX 3’-Fluoro-3’deoxythymidine triphosphate troponin T 263-268 (FLT-TP) inhibition of reverse yeast 111, 113-115 transcriptase with AZT-TP 90, 91 HIV 85, 86 5-Fluorouracil (5-FU) induction by insulin inhibition of dTMP synthase 14, 50 albumin 188 synergism with AZT 50, 51 amylase 188, 190 loci of action 14 casein 188 Folate fatty acid synthetase 186, 188 antagonists, diamino pyrimidine c-fos 186, 187, 190 derivatives 435, 440 regulatory sequences 190 -containing cofactors, reactions of 438 glyceraldehyde 3-phosphate on growth inhibition by dehydrogenase 186, 188, 190 pyrimethamine 434 a2p globulin 187 Folylpolyglutamate synthetase (FPGS, EC glucokinase 187 6.3.2.17) lipoprotein lipase 188 assay 15 c-myc 186, 187 substituted dideazafolate analogs as ovalbumin 188 substrates 14 p33 187 effects of polyglutamation 19-21, 23 prolactin 188 Fructose-1,6-bisphosphatase (F1,6P,ase, tyrosine aminotransferase 187 EC 3.1.3.11) gene, negative regulation regulation by insulin 189 alternative splicing and 261, 277, 278 during rat hepatocarcinogenesis 319-324 Gene including Oncogene I(2)gl 339-349 amplification negative by insulin in tumor cells 329 F1,6P,ase 189 as element in progression 336 GH_ 189, 190 MYCL in small cell lung cancer 330, glucagon 189 331 PDI 189 MYCN phosphoenolpyruvate carboxykinase expression and 330, 331 biological activity 332 regulatory sequence alignment 190 response to transcription differentiation-including by dioxin 307 signals 331 insulin on 186 tumorigenesis 332 long-term induction 188 in HSR regions 333, 334 negative regulation 189 in human neuroblastoma 330, 331 short-term induction 187 as prognostic parameter 334, 335 Glucagon model of 333 gene, negative regulation by structural arrangement by DNA insulin 187, 189 electrophoresis 332, 333 in glycogen synthase control 109 expression Glucocorticoid receptor in rat liver alternative splicing in 261, 262 activation developmental regulation 266, 267 5-azacytidine on 256 induced by 5-azacytidine 247 mechanism 256 insulin regulation of 185-191 5-azacytidine on 253-255, 257 modulation by DAG generation 296 chromatography of 256, 257 myc tiazofurin on 46, 62, 63, 65 determination 248, 249 MYCN Glucokinase (EC 2.7.1.1) gene induction amplification and 330-332 by insulin 187 unamplified in undifferentiated Glucose utilization cells 330, 331 in various cells 236, 237 protein kinase Con 298 pathways, control of 227 ras, TRon 46, 62, 63, 65 Glucose 6-phosphatase (EC 3.1.3.9) a-tropomyosin 263, 268-274 insensitivity to 5-azacytidine 249, 250 SUBJECT INDEX Glutamate production in various cells 237 metabolism Glutaminase (EC 3.5.1.2) activities in in yeast 112 neoplastic cells 243 possible role of glucose-6-P 112, Glutamine 113 release from muscle in cancer signal transduction and 101-115 patients 244 storage in yeast 112 utilization synthesis, enzymology of 102 branched pathway control and 232 Glycogen kinase 3 (GSK-3) in various cells 236, 237 phosphorylation rate and biosynthetic of glycogen synthase 105, 106 requirements 231, 243 sites 107-109 role in precise metabolic Glycogen synthase (EC 2.4.1.11) control 243, 245 catalysis of elongation phase 102 Glutaminolytic pathways, oxidative and evolution of phosphorylation control biosynthetic branches 233 in 114 role in precise metabolic control 233, homologies 103, 104 243, 245 mammalian 103, 104 Glutathione transferase 7 (GST-7, control of 109 EC 2.5.1.12) in resistant human homology with yeast 113 tumors 319 in vitro modification 104 Glutathione transferase P (GST-P, EC ordered phosphorylation 106, 115 2.5.1.12) phosphorylation model 105 expression in rat tumors 319 regulatory regions of 108 during hepatocarcinogenesis 319 multiple site phosphorylation 103 gene yeast 109 cloning 320 genes 113-115 connection to CAT gene 320 phosphorylation sites 114 introduction into normal rat liver polypeptides of 113-115 cells and 324 purification 113 enhancer region I (GPEI) 320 similarities to mammalian 111-113, enhancement by cooperativity of 115 palindromic TREs 322, 323 Glycogen synthase of E.coli (EC 2.4.1.21) c-jun level of cell and 322 relation to eukaryotic form 103, structure, TRE-like sequence 321, 104 322 Glycogenin regulatory sequences cDNA for 102 enhancer regions 320, 321 homology with promoter region, details 320, 321 UDP-glucuronosyltransferase 104 silencer region 320, 321 self-glucosylating capacity 102 TPA responsive element Glycolysis (TRE) 320, 321 in normal and neoplastic cells 240 structural analysis 320 oxidative and biosynthetic branches 233 Glutathione transferases (GSTs, EC rates in tumor cells 231 2.5.1.12) in detoxification of role in precise metabolic control 233 xenobiotics 319 Glycosaminoglycans binding to lipoprotein Glyceraldehyde-3-phosphate dehydrogenase lipase 196 (GAPDH, EC 1.2.1.12) GMP synthase (EC 6.3.5.2) activity gene induction by insulin 186, 188 increase in cancer cells 52 regulatory sequences 190, 191 GTP biosynthesis in cancer cells de novo Glycerol in rats, heparin on 211 and salvage pathways 58 Glycerol 3-phosphate dehydrogenase Guanine in fish scales 438 (EC 1.1.1.8) marker of adipocyte Guanine phosphoribosyltransferase differentiation 197 (GPRT, EC 2.4.2.8) Glycerolipid synthesis in rats, heparin activity increase in cancer cells 52 on 210-213 inhibition by allopurinol 57, 64 Glycogen Guanosine-3’ ,5'-cyclophosphate (CGMP) accumulation, signals for 109 second messenger role 351 472 SUBJECT INDEX Heart, heparin on lipoprotein lipase fibroblast MRCS cells, glycolytic and activity 209 Krebs cycle enzyme activities 238, Heparin 239 chronic administration 199, 200, growth hormone (GH) gene, negative 204-216 regulation by insulin 189 on circulating lipoprotein lipase 216 regulatory sequences 190 human therapy studies 198, 199 HeLa cells on CAT activity enhancement by cholesterol concentrations 205 cooperative TREs 323 lipoprotein lipase and hepatic culture 418 triacylglycerol lipase activities respiratory-synticial virus infection 204, 205, 216 419 triacylglycerol level 204, 205, 216 HeLa hybrid cells, glycolytic and Krebs long-term treatment effects 198 cycle enzyme activities 238, 239 rat studies 200 immunodeficiency virus (HIV) on env gene 85, 86 body weight 205, 206 gag gene 85, 86 food consumption 205-207 genome glycerolipid synthesis 210-213 composition 85 hepatic triacylglycerol secretion proteins encoded 85, 86 214 structure 86 serum lipolytic activity 206, 207 infection triacylglycerol 210, 211, 217 inhibition by trypstatin analogs 92, release of 93 hepatic triacylglycerol lipase 198, lack of vertical transmission 93, 94 215 protein gp 120 role 92 lipoprotein lipase 196-198, 206-208, inhibition 85-94 215 by AZT 47 Hepatic triacylglycerol lipase (HTGL, EC pol gene 85, 86 3.1.1.3) replication, inhibition by relation to lipoprotein lipase 196 nucleoside analogs 87-91, 94 release by heparin 198 peptides 93, 94 in human subjects 204, 205 leukemia cells HL-60 in rats 209, 210 oncogene regulation by TR 63 3,3’ ,4,4’ ,5,5’-Hexachlorobiphenyl, TdRK and dTPMS activities in 49, 65 environmental concern 307, 308 leukemia cells K562 Hexokinase (EC 2.7.1.1) oncogene regulation by tiazofurin 63 in glucose transport control 227 thymidine kinase and dTMP synthase maximum activities in various activities in 49, 65 cells 238-240, 245 leukemias Hormones on tyrosine aminotransferase clinical tiazofurin and allopurinol and serine dehydratase induction in treatment 57-65 liver 251, 253 oncogene down-regulation in 64, Human 65 brain synapsin I from 352 clinical tiazofurin treatment 53, 55 colon carcinoma cells HT-29 on CGL in blast crisis 56, 57 protection by TdR and hypoxanthine 6-mercaptopurine on 436 from MTX and AZT 51 lung carcinoma UCLA-P3 cells thymidine kinase and dTMP synthase antibody binding to 8 activities in 49, 65 MTX-Ala cytotoxicity 8 cytochrome P450,7, on steroid CP-A/KS1/4 conjugate on 9, 10 metabolism 371, 372 MTX cytotoxicity 8 cytochrome P450s insertion into yeast lymphoblastoid W1L2 cells growth cells 380 inhibition by ICI 198583 analogs 17 epithelial H.Ep.2 cells, glycolytic and of Cl line 18 Krebs cycle enzyme activities 236, lymphocyte H9 cells infection with 238, 239 HIV-1 88 SUBJECT INDEX lymphocyte-derived Daudi cells, IMP dehydrogenase (IMPDH, EC glycolytic and Krebs cycle enzyme 1.1.1.205) activities 238, 239 activity increase in neural tumors, MYCN amplication human leukemia cells 51-53 in 332 rat hepatoma 3924A cells 51, 52 neuroblastoma rat sarcoma cells 51, 52 chromosomal abnormalities 329, 330, chemotherapy target 52 332 inhibition by TR 53, 54, 57, 58, 63, 65 MYCN gene amplification in 330-335 IMPY see 2,3-Dihydro-lh- progression and MYCN gene imidazo(1,2-b)pyrazole expression 329-336 Influenza virus strains risk groups and MYCN antisense oligos on 427 amplification 334, 335 maintenance 418 ovarian carcinoma reproduction in MDCK cells cell lines inhibition by antibodies 421-423 cisplatin-resistant 40, 41 kinetics of 424 culture 34, 35 antibodies on 424 Pt drug cytotoxicity assay 35 RNA loop-forming site, antisense xenografts copying 426 culture and assay 34 modified oligo binding to 428 Pt-sensitive, Pt drug Inositol lipid comparison 37-39 phosphorylation 399-413 Hydrophobization of -PKC signalling system in nucleus 400 antibodies Inositol phosphates release after effect on virus within cell 425 phosphorylation of PI in nuclei 410 penetration into infected cells 424 Inositol-1,4,5-triphosphate second possible chemotherapy 426 messenger role 351 oligos 427, 428 Insect cells, P450s expressed in 377 N-Hydroxy-N’-aminoguanidine isoquinoline Insulin on L1210 HU-7 cells 80 in glycogen synthase control 109 17-Hydroxypregnenolone 17,20-lyase induced differentiation of 3T3 reaction rate, P450 of various cells 201-204, 214, 215, 217 species 373 on 17-Hydroxyprogesterone 17,20-lyase gene transcription 186 reaction rate, P450 of various long-term induction 188 species 373 negative regulation 189 Hydroxyurea (HU) short-term induction 187 Amidox comparison 80 lipoprotein lipase levels 196 on mRNA transport 185, 186 L1210 cell growth 74, 75 regulation of gene expression 185-191 L1210HU-7 cell growth 74, 75 regulatory element A (IRE A) 190 dNTP pools 80 regulatory sequences (IRS) 187, 190, Hypoxanthine (HX) 191 allopurinol-induced rise in plasma Iproplatin (cis-dichloro-trans- level 57, 58, 64 dihydroxy-cis-bis(isopropylamine) competitive inhibition of GPRT 54, 57 platinum(V)) concentration required 57 in experimental chemotherapy 31 protection from MTX + AZT 51 on human ovarian carcinoma xenografts 37-39 ICI 198583 see Isocitrate dehydrogenase, NAD*+-linked 2-Desamino-2-methyl-N!°-propargyl-5, (EC 1.1.1.41) and NADP*-linked (EC 8-dideazafolic acid 1.1.1.42) maximum activities in various ICI D1694 see under 2-Desamino-2- cells 238, 239, 242, 243, 245 methyl-N!°-propargyl-5 ,8-dideazafolic acid Krebs cycle enzymes, maximum Immunosuppression, 6-mercaptopurine activities in normal and neoplastic action 436, 437 cells 241-243 474 SUBJECT INDEX Lactate production in various cells 237 in human subjects 204, 205 Lactate dehydrogenase (EC 1.1.1.27) in rats 206-208 maximum activities in various cells acute dose on 209, 210 238-240 clearance of 209 Lethal (2) giant larvae (I(2)gl) gene of tissues 209 Drosophila melanogaster 339-349 Lipoprotein modulation by phenobarbital cis-regulatory elements 344 and heparin 195-217 codon usage 346, 347 Liposomes used in nuclear uptake of cDNA sequences 341,342 PI 404, 406, 407 expression Lipoxygenase (EC 1.13.11.12) activity, exon III-B requirement 342 inhibitors of 392, 393 mRNA decay, regulation and 344-347 temporal and spatial pattern 342-344 MAIOQ see 4-Methyl-5-aminoisoquinoline homozygous mutations 339 thiosemicarbazone malignancies from 339 Manganese in infectivity 435 5’-moiety organization 341 Mardin-Derby canine kidney cells see Dog nucleotide sequence, size of 340 kidney (MDCK) cells P-element transposons 341, 345 Membrane see Designer membrane transcription initiation 340 6-Mercaptopurine (6-MP) transcriptional organization 340, 348 as antileukemic 436 translation initiation site 342 immunosuppressive activity 436 Lethal (2) giant larvae (I(2)gl) Metabolic-control logic 225 proteins application to binding to plasma membrane 343, branched pathways 232, 234, 244 347-349 cachexia 244 functional relevance 348 cellular fuel/energy production in transgenic animals 345 236-244 cellular distribution 343, 349 branched-point sensitivity 233, 243 phosphorylation sites 347 external effectors 230 post-translational modifications 347 flux generating step 227, 235, 244 mRNA hexokinase reaction 227, 230 codon usage on translation near-equilibrium reactions 226, 227, 235 efficiency 346, 347 non-equilibrium reactions 226, 227 decay, in regulation of gene allosteric control 235 expression 344, 345 phosphofructokinase reaction 230 destabilization, AU-rich regions pyruvate kinase reaction 229, 230 and 345, 346 regulators 228-231 two size classes 344, 345 regulatory effectors 233, 234 Lipid kinases, nuclear membrane site 412, requirements for quantitative enzyme 413 information 235, 236 Lipoprotein lipase (LPL, EC 3.1.1.34) second messengers 228 activity in differentiating 3T3 Metabolic pathway cells 201-204, 214 branched adipocyte differentiation and 197 control of flux 234, 235, 244 assay 196, 199 glutaminolysis 232, 233 binding of glycolysis 233 apolipoprotein C-II 196 role in cell division 231-233 glycosaminoglycans 196 definition, physiologically related 227 catalytic mechanism 196 enzyme activity as measure of flux 235 distribution 195 linear, flux transmission in 227-231 function 195 Methotrexate (MTX) gene induction by insulin 188 competition with ICI 198583 19 phenobarbital on availability 197, 204, in combination with AZT 50-52 214 inhibition of regulation in fasting state 196, 197 DHFR 13, 18 release by heparin 196-198 dTMP synthase 50