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Index

Acridine orange, 51, 85, 168, 186, Cell 260, 268, 271, 298-316 doubling time (T^), 56, 74-77 Actinomycin D, 52, 256, 257, 259, population heterogeneity, 15, 34, 263, 273, 330 37, 40, 102, 193, 231, 232 Anthracyclines, 337-366 sorting, 74, 75, 82-85, 94, 95,101- adriamycin, 57-59, 64, 179, 337, 105, 114, 127, 148, 173, 371 338, 341-356 Cell cycle daunomycin, 337, 338, 341-356 asynchronous populations, 1, 97- other, 341-345 99, 102, 105, 106, 111, 112, resistance, 349-356 174, 231-238, 305-313, 317- transport, 342-356 328 Ara-C (see arabinoside) duration (T^), 32-44, 49, 56, 64, Autoradiography, 1-24, 31-44, 47- n, 102, 103, 127, 317-328, 55, 65, n, 104, 112, 114, 125, 372-395 144, 146, 148, 263, 291 perturbed populations, 120-126, artifacts, 10, 11, 14 1Z%-1M, 309-313 background, 11, 15, 16-20 recruitment, 42, 43, 57, 58, 63-66, chemography, 21-23 79, 81, 93, 99, 105, 106, 111, standards, 21 112, 207, 208, 238-249 Azacytidine (dihydroxy-5-azacyti- Centrifugal elutriation (see Elutria- dine), 259, 263, 310, 311 tion) , 48, 59, 61, 62, 73, Bleomycin, 82 86, 150, 207-209, 238-247, 275, Bone marrow, 126, 127, 129-131, 310-316, 330, 331 185, 198, 207, 266, 340, 351 terminal point of drug action, Bromodeoxyuridine (BrdUrd), 51, 313, 330 107-132,139,176,196-198, 273- 275, 292 Chinese hamster ovary cells antibodies. 111, 112, 197 (CHO), 94, 98, 105-111, 120- BrdUrd/DNA analysis, 111-131, 126, 177, 182, 189, 192-198, 212, 209, 210, 216-219, 241-247, 217-219, 232, 233, 237, 259, 268, 273 295, 296, 303-305, 307, 352, 358, Butyrate (n-butyrate), 258, 259, 263, 367-398 268, 311, 314, 330 Chromatin condensation, 51, 183, 260-263, 270-276, 292, 296, 314- Carcinogenesis, 1 316, 329

403 404 Index

Chromomycin A3 (CA3), 94, 101, 145, 148,152-156, 171, 173, 175, 127, 168, 179, 181 180, 186, 188, 192, 193, 198 Clonogenic cells (clonogens), 65, phase fractions, 95-104, 210-231 73-87, 256, 266-268, 275 asynchronous populations, 96- Clonogenicity, 1, 58, 60-62, 65, 84- 98, 210-216, 218-225 86, 93, 111, 139, 140, 145, 150, fitting methods, 218-231 153-156, 351 graphical methods, 212-218 Cclcemid, 105, 107, 182, 193, 194, perturbed populations, 98, 99, 293, 295, 303 225-231, 369-398 Colchicine, 293, 295 Cyanine dyes, 269 Ellipticine, 259 Cyclin (PCNA), 276 Elutriation, centrifugal, 74, 84, 85, Cyclohexamide, 256 114, 263, 370 Cyclophosphamide, 58, 59, 62-64, Ethidium bromide (EB), 52, 165, 67 167, 168, 171, 180, 181, 272 Cytosine arabinoside (ara-C), 52, 57, 66, 103, 105, 120-124, 126- Feulgen reaction, 11, 163, 170, 175 129,131,179, 207-210, 230, 238- Flow cytometry (FCM), 7, 8, 51, 57, 247, 256, 259 66, 74, 75, 82, 85, 93-133, 139- 145,150,154,155,163-167,170- DAPI (4,6-diamidino-2-phenyl- 176,181,194,195, 257, 264-278, indole), 168, 171, 175, 176, 186 292, 300-301, 337-345, 369, 371 Density gradient, 74, 83, 84 Fluorescein isothiocyanate (FITC), Differentiation, 35, 37, 50, 93, 126, 169, 184-190, 197 132, 147, 148 5-Fluorouracil (5-FU), 60, 62 Dihydrofoleate reductase (DHFR), Fraction of labeled mitoses (FLM) 277, 356-361 [see Percent of labeled mitoses (DHAQ), (PLM)] 310, 311, 314 Dividing cells, fraction {see Non- GO cells (also see Nondividing cells), dividing cells) 7, 31, 34-38, 42, 43, 52,118, 255, DNA 256, 264, 278 denaturation, 51, 112, 113, 125, Gl-phase, 3, 7, 35, 37, 50-52, 74, 126, 170, 260-264, 270-272 82-84, 93-105, 109, 110, 114, polymerase, 51 115,118-120,124,127,132, 144, synthesis 146, 148, 167, 179, 192, 193, replication, 3, 7, 23, 31, 44, 49, 201-231, 258-267, 301-313, 352- 50, 74, 82, 109, 112, 127, 354 129, 193, 273, 274, 291, 292 duration (Tg,), 32, 49, 97, 99,102, rate, 15,112, 120,124,125, 216, 103, 106, 108, 111, 112, 120, 219, 291 146, 232-247, 305-309, 317- DNA damage, 351 330, 382, 392 DNA distribution analysis, 7, 50, G2-phase, 3, 7, 50, 51, 82, 85, 93, 51, 74-76, 82-84, 106, 107, 139, 96-105, 110, 114, 115, 118-120, Index 405

124,127,132,144,146,148,167, Lymphocytes, 8, 50-52, 94, 105, 184, 201-231, 305-313, 352-354 108,109,154,176,180,194, 255, duration (Tg2), 32, 49, 97, 99,102, 256, 260, 264-271, 297, 359 103, 106, 108, 111, 112, 120,, stimulation, 51, 52, 194 146, 232-247, 307, 317-30, Lymphoma (AKR), 17, 18 382-392 Gene amplification, 275 Mathematical models Granulocytes, 256 BrdUrd/DNA distributions, 216- Growth fraction {see Nondividing 218, 245-249 cells) DNA distributions, 210-215, 218- 231, 239-244, 382-392 HeLa cells, 261, 267, 268, 271 growth curves, 231, 232 Hepatocytes, 256 least-squares best fit, 219-222, Histones, 270, 278, 314, 329 398, 399 Hoechst PLM curves, 36-42, 232-237 33258,107-110,130,175,176,181, RC curves, 237, 238 197, 273, 375 stathmokinetic curves, 317-328 33342, 82,113,127,129, 168, 176, Methotrexate (MTX), 256, 264, 277 177, 182-189, 194-198, 268, MTX-FITC, 357-361 343, 371 resistance, 358-361 Hydroxyurea (HU), 52, 59, 61, 74, transport, 356-359 79, 80-82, 264, 331, 369, 370 Mithramycin, 168, 171, 179, 181, Hypoxic cells, 74, 82, 257, 259, 272, 184, 185, 197, 198, 273 278 Mitochondria, 193-196, 257-259, 269, 274 Mitotic index (MI), 58, 59 Intestinal cells, 147-151, 295 M-phase Isoleucine, 256, 268 cells, 3, 31-44, 48, 52, 82-85, 96- 99, 105, 107, 114, 118-120, Labeling index (LI), 1-24, 35, 38, 50, 127, 132, 144, 146, 148, 155, 52, 55, 59, 60, 66, 81, 86, 104, 173, 182-184, 274, 291-336 112, 147-150, 154, 243-246 duration (T^), 32, 99-101, 106, Leukemia, 40, 41, 53, 94 108-112, 120, 124, 146 AK, 13 CML, 258, 271 Nerve cells, 256 Friend erythroleukemia, 183, 184, NIH-3T3 cells, 258, 259, 265, 268, 194, 258, 261, 270, 271, 351 276 HL60, 183, 184, 194, 270 Nondividing cells L1210, 125, 126, 194, 213-215, chromatin structure, 270-273 223-226, 228, 270, 272, 276, clonogenicity, 74-79 307, 314, 352-354 growth fraction, 4, 34, 35, 42, 47- P388, 343, 350, 354-362 67, 105, 106, 174 Light scatter, 187, 188, 266, 339, metabolic properties, 257-264 343, 345, 352-355 mitochondrial probes, 269, 270 406 Index

protein content, 267 Radioactivity per cell method (RC), quiescent cells 99-105, 209, 237, 238 GIQ, 188, 258, 260, 268-271, Radioautography {see Autoradio­ 274 graphy) SQ, G2Q, 258, 260, 261, 269, Radiotherapy, 48 271 Resting cells {see Nondividing cells) GID, 258, 261, 274 Retinoic acid, 263, 330 GIA, 259-262, 268-272, 278, Rhodamine 123, 168, 193-195, 301-303, 307-309, 312, 331 260-263, 269-272, 275, 311, 330, G1-, S-, G2M-arrested, 259 340 RNA content, 192, 194, 268, 269 RNA content, 51, 85, 113, 164, 167, size, 264-267 174,186,188,192-198, 257-263, Nucleoli, 50, 65 267-270, 274 Nuclear proteins, 277 S-phase, 1, 4, 31, 50-53, 58-61, 74, Olivomycin, 168, 179 79-85, 93, 95-103,112,114-120, Oncogenes, 275, 276 124,127,129,132,140,144,146, 148, 150, 153, 154, 167, 173, PCNA {see Cyclin) 196-198, 201-231, 258-261, 267, Percent labeled mitoses (PLM), 4, 309-313, 352-354, 358 10, 31-44, 65, 99, 105, 232-237, duration (Ts), 32, 35, 38, 49, 50, 296 99, 102, 106, 108, 111, 112, Plating efficiency {see Clonogenic- 120, 146, 232-247, 309, 317- ity) 328, 382-392 Poisson distribution, 17, 19 Spheroids, 256, 268, 269, 352 Primer-available DNA-dependent Stathmokinesis, 105, 291-336 DNA polymerase index (PDP Stem cells (see Clonogenic cells) index), 51, 52 Synchrony, 48, 84, 97,100,103,127, Proliferative fraction {see Nondivid- 207-208, 329, 367-402 ing cells) analysis of, 369 Propidium iodide (PI), 113, 165- cell sorting, 371 168, 177, 182-185, 197, 198 elutriation, 370, 371 Protein content, 164, 167, 174, 180, mitotic selection, 369, 370 185-188,192-198, 257-259, 263, 264 Pyronin Y, 163, 164, 186, 189, 194, Thymidine 195, 268 endogeneous pool, 5, 108, 114, 118, 119, 197, 291 Quiescent cells (Q) {see Nondivid- kinase, 5, 6 ing cells) transport, 10 Tissue dispersal, 51, 76, 82, 94, 103, Radiation, 11, 57, 61, 75, 77, 78, 81, 139-156 82, 85, 93, 146, 198, 297 chemical, 139-143, 147 Index 407

enzymatic, 82,139, 140-147,151- RIF, 54, 61, 66 154 mechanical, 139, 142-144, 151- Unbalanced growth, 259, 261, 263 154 Tritiated thymidine ('H-TdR), 1-23, Vinblastin, 293, 295, 314 31-44, 47-67, 74, 101-103, 112, Vincristin, 293, 295 127,128, 132,139, 146-148,173, 186 continuous labeling, 11, 49, 50, 65, 66, 77 labeled microcolonies, 75-79 pulse labeling, 2, 31, 32, 48, 49, 64, 66, 81,103,106, 209, 232- 234, 237, 291 specific activity, % 12, 74, 79, 80 Tumor growth fraction (see Non- dividing cells) Tumor necrosis factor, 316 Tumors adenocarcinoma, 13, 14 EMT6, 80, 84, 85, 151, 268, 352 experimental, 1, 47, 49-51, 55, 57, 64, 67, 73, 74, 271, 272 fibrosarcoma, 53, 54, 84, 151 glioma, 53, 54 hepatoma, 63 human, 40-42, 57, 86, 151, 153, 154, 296, 361 Lewis lung, 13, 53, 54, 63, 103, 104 mammary, 13, 14, 51, 53-55, 57, 58, 63, 85, 155 mastocytoma, 63 melanoma, 8, 13, 14, 40, 41 plasmacytoma, 13, 14 rat brain, 84-86, 118, 119 rhabdmyosarcoma, 57, 86, 151 sarcomas, 52, 54 KHT, 82-86, 101,103,106, 118, 120, 126, 128,140, 151,156, 230, 238-247 osteogenic (Ridgeway), 8, 9,12, 13