The use of in vitro systems to assess cancer mechanisms and the carcinogenic potential of chemicals

Alternatives to Laboratory Animals

Volumn 39, Issue 3, 2011, Pages 233-255

  Breheny, Damien ^a   Oke, Oluwatobiloba ^a   Faux, Stephen P ^a  

^a BRITISH AMERICAN TOBACCO   (United Kingdom)

Author keywords

Carcinogenesis; Cell transformation; Cigarette smoke; Genotoxicity; REACH

Indexed keywords

CIGARETTE SMOKE; TELOMERASE;

ANGIOGENESIS; APOPTOSIS; CANCER CELL; CARCINOGENESIS; CELL INVASION; CELL MIGRATION; CELL PROLIFERATION; CELL TRANSFORMATION; CHEMICAL CARCINOGENESIS; DISEASE COURSE; DISEASE MARKER; ENZYME ACTIVITY; GENOTOXICITY; HUMAN; IN VITRO STUDY; NONHUMAN; PRIORITY JOURNAL; REVIEW;

EID: 79960926536     PISSN: 02611929     EISSN: None     Source Type: Journal    
DOI: 10.1177/026119291103900301     Document Type: Review

References (181)

1. Hanahan, D. & Weinberg, R.A. (2000). The hallmarks of cancer. Cell 100, 57-70. (Pubitemid 30046295)
2. Hahn, W.C. & Weinberg, R.A. (2002). Rules for making human tumor cells. New England Journal of Medicine 347, 1593-1603. (Pubitemid 35315841)
3. Katoh, M. (2007). Networking of WNT, FGF, Notch, BMP, and Hedgehog signaling pathways during carcinogenesis. Stem Cell Reviews 3, 30-38.
4. Mitra, A.P., Datar, R.H. & Cote, R.J. (2006). Molecular pathways in invasive bladder cancer: New insights into mechanisms, progression, and target identification. Journal of Clinical Oncology 24, 5552-5564. (Pubitemid 46631336)
5. Shchors, K. & Evan, G. (2007). Tumor angio-genesis: Cause or consequence of cancer? Cancer Research 67, 7059-7061. (Pubitemid 47206529)
6. Deelman, H.T. (1927). The part played by injury and repair in the development of cancer: With remarks on the growth of exposal cancer. British Medical Journal 1, 872-878.
7. Yamagiwa, K. & Ichikawa, K. (1915). Experimentelle Studie über die Pathogenese der Epithelial-geschwülste. Mitteilungen der Medizinischen Fak ul tat, Universitat Tokio [Transactions of the Medical Faculty, Imperial University, Tokyo] 15, 295-344.
8. Cohen, S.M. (2004). Human carcinogenic risk evaluation: An alternative approach to the twoyear rodent bioassay. Toxicological Sciences 80, 225-229.
9. Knight, D.J. & Breheny, D. (2002). Alternatives to animal testing in the safety evaluation of products. ATLA 30, 7-22. (Pubitemid 34174869)
10. Russell, W.M.S. & Burch, R.L. (1959). The Principles of Humane Experimental Technique, 238pp. London, UK: Methuen.
11. ECVAM (2008). Genotoxicity and Carcinogenicity. Ispra, Italy: European Centre for the Validation of Alternative Methods, Institute for Health and Consumer Protection, Joint Research Centre. Available at: http://ecvam.jrc.it/ index.htm (Accessed 08.09.08).
12. Bhogal, N., Grindon, C., Combes, R. & Balls, M. (2005). Toxicity testing: Creating a revolution based on new technologies. Trends in Biotechnology 23, 299-307. (Pubitemid 40726271)
13. Anon. (2003). Directive 2003/15/EC of the European Parliamennd of the Council of 27 February 2003 amending Council Directive 76/768/ EEC on the approximation of the laws of the Member States relating to cosmetic products. Official Journal of the European Union L66, 11.3.2003, 26-35.
14. Ellinger-Ziegelbauer, H., Aubrecht, J., Kleinjans, J.C. & Ahr, H.J. (2008). Application of toxicogenomics to study mechanisms of genotoxicity and carcinogenicity. Toxicology Letters 186, 36-44.
15. Anon. (2006). Regulation (EC) No 1907/2006 of the European Parliament and of the Council of 18 December 2006 concerning the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH), establishing a European Chemicals Agency, amending Directive 1999/45/EC and repealing Council Regulation (EEC) No 793/93 and Commission Regulation (EC) No 1488/94 as well as Council Directive 76/769/EEC and Commission Directives 91/155/EEC, 93/67/EEC, 93/105/EC and 2000/21/EC. Official Journal of the European Union L396, 30.12.2006, 1-849.
16. OECD (2010). OECD Draft Guidance Document No. 116 on the Design and Conduct of Chronic Toxicity and Carcinogenicity Studies, Supporting TG 451, 452, 453. Full draft 17 December 2010, 136pp. Paris, France: Organisation for Economic Co-operation and Development. Available at: http://www.oecd.org/ dataoecd/24/49/46766792.pdf (Accessed 17.05.11).
17. Barrett, J.C. & Ts'o, P.O. (1978). Evidence for the progressive nature of neoplastic transformation in vitro. Proceedings of the National Academy of Sciences of the USA 75, 3761-3765. (Pubitemid 8399280)
18. ICH (2008). Draft Consensus Guideline: Guidance on Genotoxicity Testing and Data Interpretation for Pharmaceuticals Intended for Human Use. S2(R1). Current Step 2 version dated 6 March 2008, 32pp. Geneva, Switzerland: International Conference on Harmonisation. Available at: http://www.ich.org/ products/guidelines/safety/article/safety-guidelines.html (Accessed 19.05.11).
19. Johnson, M.D., Schilz, J., Djordjevic, M.V., Rice, J.R. & Shields, P.G. (2009). Evaluation of in vitro assays for assessing the toxicity of cigarette smoke and smokeless tobacco. Cancer Epidemiology Biomarkers & Prevention 18, 3263-3304.
20. Thybaud, V., Aardema, M., Clements, J., Dearfield, K., Galloway, S., Hayashi, M., Jacobson-Kram, D., Kirkland, D., MacGregor, J.T., Marzin, D., Ohyama, W., Schuler, M., Suzuki, H. & Zeiger, E. (2007). Strategy for genotoxicity testing: Hazard identification and risk assessment in relation to in vitro testing. Mutation Research 627, 41-58. (Pubitemid 46091766)
21. ECHA (2008). Guidance on Information Requirements and Chemical Safety Assessment. Chapter R.7a: Endpoint Specific Guidance, pp. 374-428. Helsinki, Finland: European Chemicals Agency. Available at: http://guidance.echa.europa. eu/docs/guidance-document/information-requirements-r7a-en.pdf (Accessed 19.05.11).
22. ICH (1997). Genotoxicity: A Standard Battery for the Genotoxicity Testing of Pharmaceuticals. S2B. Current Step 4 version dated 16 July 1997, 11pp. Geneva, Switzerland: International Conference on Harmonisation. Available at: http://www.ich.org/products/guidelines/safety/article/safety-guidelines. html (Accessed 19.05.11).
23. Maron, D.M. & Ames, B.N. (1983). Revised methods for the Salmonella mutagenicity test. Mutation Research 113, 173-215. (Pubitemid 13120319)
24. Kirsch-Volders, M., Sofuni, T., Aardema, M., Albertini, S., Eastmond, D., Fenech, M., Ishidate, M., Jr, Lorge, E., Norppa, H., Surrallés, J., von der Hude, W. & Wakata, A. (2000). Report from the In Vitro Micronucleus Assay Working Group. Environmental & Molecular Mutagenesis 35, 167-172. (Pubitemid 30196660)
25. Clive, D. & Spector, J.F. (1975). Laboratory procedure for assessing specific locus mutations at the TK locus in cultured L5178Y mouse lymphoma cells. Mutation Research 31, 17-29.
26. Pfuhler, S., Kirst, A., Aardema, M., Banduhn, N., Goebel, C., Araki, D., Costabel-Farkas, M., Dufour, E., Fautz, R., Harvey, J., Hewitt, N.J., Hibatallah, J., Carmichael, P., Macfarlane, M., Reisinger, K., Rowland, J., Schellauf, F., Schepky, A. & Scheel, J. (2010). A tiered approach to the use of alternatives to animal testing for the safety assessment of cosmetics: Genotoxicity. A COLIPA analysis. Regulatory Toxicology & Pharmacology 57, 315-324.
27. Aardema, M.J., Barnett, B.C., Khambatta, Z., Reisinger, K., Ouedraogo-Arras, G., Faquet, B., Ginestet, A.C., Mun, G.C., Dahl, E.L., Hewitt, N.J., Corvi, R. & Curren, R.D. (2010). International prevalidation studies of the EpiDerm 3D human reconstructed skin micronucleus (RSMN) assay: Trans ferability and reproducibility. Mutation Research 701, 123-131.
28. LeBoeuf, R.A., Kerckaert, G.A., Aardema, M.J. & Gibson, D.P. (1990). Multistage neoplastic transformation of Syrian hamster embryo cells cultured at pH 6.70. Cancer Research 50, 3722-3729. (Pubitemid 20194122)
29. Berwald, Y. & Sachs, L. (1963). In vitro cell transformation with chemical carcinogens. Nature, London 200, 1182-1184.
30. Das, A., Bhattacharya, A. & Chakrabarti, G. (2009). Cigarette smoke extract induces disruption of structure and function of tubulin-microtubule in lung epithelium cells and in vitro. Chemical Research in Toxicology 22, 446-459.
31. Hays, L.E., Zodrow, D.M., Yates, J.E., Deffebach, M.E., Jacoby, D.B., Olson, S.B., Pankow, J.F. & Bagby, G.C. (2008). Cigarette smoke induces genetic instability in airway epithelial cells by suppressing FANCD2 expression. British Journal of Cancer 98, 1653-1661. (Pubitemid 351684688)
32. Kakunaga, T. (1985). Critical review of the use of established cell lines for in vitro cell transformation. IARC Scientific Publications 67, 55-73.
33. Loeb, L.A. & Harris, C.C. (2008). Advances in chemical carcinogenesis: A historical review and prospective. Cancer Research 68, 6863-6872.
34. Barrett, J.C., Hesterberg, T.W. & Thomassen, D.G. (1984). Use of cell transformation systems for carcinogenicity testing and mechanistic studies of carcinogenesis. Pharmacology Reviews 36, 53S-70S.
35. Kang, M.K. & Park, N.H. (2001). Conversion of normal to malignant phenotype: Telomere shortening, telomerase activation, and genomic instability during immortalization of human oral keratinocytes. Critical Reviews in Oral Biology & Medicine 12, 38-54. (Pubitemid 32374283)
36. Nettesheim, P. & Barrett, J.C. (1985). In vitro transformation of rat tracheal epithelial cells: A model for the study of multistage carcinogenesis. Carcinogenesis: A Comprehensive Survey 9, 283-291.
37. Newbold, R.F. (1985). Malignant transformation of mammalian cells in culture: Delineation of stages and role of cellular oncogene activation. IARC Scientific Publications 67, 31-53.
38. Yamasaki, H., Ashby, J., Bignami, M., Jongen, W., Linnainmaa, K., Newbold, R.F., Nguyen-Ba, G., Parodi, S., Rivedal, E., Schiffmann, D., Simons, J.W. & Vasseur, P. (1996). Nongenotoxic carcinogens: Development of detection methods based on mechanisms: A European project. Mutation Research 353, 47-63. (Pubitemid 26201865)
39. Barrett, J.C., Crawford, B.D., Mixter, L.O., Schechtman, L.M., Ts'o, P.O. & Pollack, R. (1979). Correlation of in vitro growth properties and tumorigenicity of Syrian hamster cell lines. Cancer Research 39, 1504-1510. (Pubitemid 9172664)
40. OECD (2007). Series on Testing and Assessment No. 31. Detailed Review Paper on Cell Transformation Assays for Detection of Chemical Carcinogens [ENV/JM/MONO(2007)18], 164pp. Paris, France: Organisation for Economic Co-operation and Development. Available at: http://www.oecd.org/document/30/0, 3746,en-2649-34377-1916638-1-1-1-1,00&&en-USS-01DBC.html (Accessed 19.05.11).
41. Combes, R., Balls, M., Curren, R., Fischbach, M., Fusenig, N., Kirkland, D., Lasne, C., Landolph, J., LeBoeuf, R., Marquardt, H., McCormick, J., Muller, L., Rivedal, E., Sabbioni, E., Tanaka, N., Vasseur, P. & Yamasaki, H. (1999). Cell transformation assays as predictors of human carcinogenicity. The report and recommendations of ECVAM Workshop 39. ATLA 27, 745-767. (Pubitemid 29503028)
42. Tsutsui, T., Tamura, Y., Suzuki, A., Hirose, Y., Kobayashi, M., Nishimura, H., Metzler, M. & Barrett, J.C. (2000). Mammalian cell transformation and aneuploidy induced by five bisphenols. International Journal of Cancer 86, 151-154. (Pubitemid 30180807)
43. Tsuchiya, T., Umeda, M., Tanaka, N., Sakai, A., Nishiyama, H., Yoshimura, I., Ajimi, S., Asada, S., Asakura, M., Baba, H., Dewa, Y., Ebe, Y., Fushiwaki, Y., Hagiwara, Y., Hamada, S., Hamamura, T., Iwase, Y., Kajiwara, Y., Kasahara, Y., Kato, Y., Kawabata, M., Kitada, E., Kaneko, K., Kizaki, Y., Kubo, K., Miura, D., Mashiko, K., Mizuhashi, F., Muramatsu, D., Nakajima, M., Nakamura, T., Oishi, H., Sasaki, T., Shimada, S., Takahashi, C., Takeda, Y., Wakuri, S., Yajima, N., Yajima, S. & Yatsushiro, T. (2010). Application of the improved BALB/c 3T3 cell transformation assay to the examination of the initiating and promoting activities of chemicals: The second interlaboratory collaborative study by the non-genotoxic carcinogen study group of Japan. ATLA 38, 11-27.
44. Sasaki, K., Mizusawa, H. & Ishidate, M. (1988). Isolation and characterization of ras-transfected BALB/3T3 clone showing morphological transformation by 12-O-tetradecanoyl-phorbol-13-acetate. [In Japanese.] Journal of Cancer Research 79, 921-930.
45. Asada, S., Sasaki, K., Tanaka, N., Takeda, K., Hayashi, M. & Umeda, M. (2005). Detection of initiating as well as promoting activity of chemicals by a novel cell transformation assay using v-Haras-transfected BALB/c 3T3 cells (Bhas 42 cells). Mutation Research 588, 7-21. (Pubitemid 41630722)
46. Ohmori, K., Umeda, M., Tanaka, N., Takagi, H., Yoshimura, I., Sasaki, K., Asasda, S., Sakai, A., Araki, H., Asakura, M., Baba, H., Fushiwaki, Y., Hamada, S., Kitou, N., Nakamura, T., Nakamura, Y., Oishi, H., Sasaki, S., Shimada, S., Tsuchiya, T., Uno, Y., Washizuka, M., Yajima, S., Yamamoto, Y., Yamamura, E. & Yatsushiro, T. (2005). An inter-laboratory collaborative study by the Non-Genotoxic Carcinogen Study Group in Japan, on a cell transformation assay for tumour promoters using Bhas 42 cells. ATLA 33, 619-639. (Pubitemid 43151818)
47. Sakai, A., Sasaki, K., Muramatsu, D., Arai, S., Endou, N., Kuroda, S., Hayashi, K., Lim, Y.M., Yamazaki, S., Umeda, M. & Tanaka, N. (2010). A Bhas 42 cell transformation assay on 98 chemicals: The characteristics and performance for the prediction of chemical carcinogenicity. Mutation Research 702, 100-122.
48. Kirkland, D.J., Henderson, L., Marzin, D., Muller, L., Parry, J.M., Speit, G., Tweats, D.J. & Williams, G.M. (2005). Testing strategies in mutagenicity and genetic toxicology: An appraisal of the guidelines of the European Scientific Committee for Cosmetics and Non-Food Products for the evaluation of hair dyes. Mutation Research 588, 88-105. (Pubitemid 41785731)
49. Harvey, J.S., Howe, J.R., Lynch, A.M. & Rees, R.W. (2005). The results of five coded compounds: Genistein, metaproterenol, rotenone, p-anisidine and resorcinol tested in the pH 6.7 Syrian hamster embryo cell morphological transformation assay. Mutagenesis 20, 51-56. (Pubitemid 40333308)
50. Boukamp, P., Petrussevska, R.T., Breitkreutz, D., Hornung, J., Markham, A. & Fusenig, N.E. (1988). Normal keratinization in a spontaneously immortalized aneuploid human keratinocyte cell line. Journal of Cell Biology 106, 761-771. (Pubitemid 18089976)
51. Fusenig, N.E. & Boukamp, P. (1998). Multiple stages and genetic alterations in immortalization, malignant transformation, and tumor progression of human skin keratinocytes. Molecular Carcino-genesis 23, 144-158. (Pubitemid 28535818)
52. Morgan, T.L., Yang, D.J., Fry, D.G., Hurlin, P.J., Kohler, S.K., Maher, V.M. & McCormick, J.J. (1991). Characteristics of an infinite life span diploid human fibroblast cell strain and a neardiploid strain arising from a clone of cells expressing a transfected v-myc oncogene. Experimental Cell Research 197, 125-136.
53. Sager, R. (1991). Senescence as a mode of tumor suppression. Environmental Health Perspectives 93, 59-62.
54. Bodnar, A.G., Ouellette, M., Frolkis, M., Holt, S.E., Chiu, C.P., Morin, G.B., Harley, C.B., Shay, J.W., Lichtsteiner, S. & Wright, W.E. (1998). Extension of life-span by introduction of telomerase into normal human cells. Science, New York 279, 349-352. (Pubitemid 28063364)
55. Bond, J.A., Haughton, M.F., Rowson, J.M., Smith, P.J., Gire, V., Wynford-Thomas, D. & Wyllie, F.S. (1999). Control of replicative life span in human cells: Barriers to clonal expansion intermediate between M1 senescence and M2 crisis. Molecular & Cellular Biology 19, 3103-3114. (Pubitemid 29144555)
56. Shay, J.W. & Wright, W.E. (1989). Quantitation of the frequency of immortalization of normal human diploid fibroblasts by SV40 large T-antigen. Experimental Cell Research 184, 109-118. (Pubitemid 19233392)
57. Hahn, W.C., Counter, C.M., Lundberg, A.S., Beijersbergen, R.L., Brooks, M.W. & Weinberg, R.A. (1999). Creation of human tumour cells with defined genetic elements. Nature, London 400, 464-468. (Pubitemid 29361801)
58. Heeg, S., Doebele, M., von Werde, A. & Opitz, O.G. (2006). In vitro transformation models: Modeling human cancer. Cell Cycle 5, 630-634.
59. Pang, Y., Li, W., Ma, R., Ji, W., Wang, Q., Li, D., Xiao, Y., Wei, Q., Lai, Y., Yang, P. Chen, L., Tang, S., Lin, Y., Zhuang, Z., Zheng, Y. & Chen, W. (2008). Development of human cell models for assessing the carcinogenic potential of chemicals. Toxicology & Applied Pharmacology 232, 478-486.
60. Benedict, W.F., Rucker, N., Faust, J. & Kouri, R.E. (1975). Malignant transformation of mouse cells by cigarette smoke condensate. Cancer Research 35, 857-860.
61. Breheny, D., Zhang, H. & Massey, E.D. (2005). Application of a two-stage Syrian hamster embryo cell transformation assay to cigarette smoke particulate matter. Mutation Research 572, 45-57. (Pubitemid 40403653)
62. Emura, M. & Mohr, U. (1983). Toxic and transforming effects of cigarette smoke condensates in fetal Syrian golden hamster lung cell cultures. International Journal of Experimental Pathology 24, 261-264. (Pubitemid 14222882)
63. Kim, M.S., Huang, Y., Lee, J., Zhong, X., Jiang, W.W., Ratovitski, E.A. & Sidransky, D. (2010). Cellular transformation by cigarette smoke extract involves alteration of glycolysis and mitochondrial function in esophageal epithelial cells. International Journal of Cancer 127, 269-281.
64. Klein-Szanto, A.J., Iizasa, T., Momiki, S., Garcia-Palazzo, I., Caamano, J., Metcalf, R., Welsh, J. & Harris, C.C. (1992). A tobacco-specific N-nitrosamine or cigarette smoke condensate causes neoplastic transformation of xenotransplanted human bronchial epithelial cells. Proceedings of the National Academy of Sciences of the USA 89, 6693-6697.
65. Lemjabbar-Alaoui, H., Dasari, V., Sidhu, S.S., Mengistab, A., Finkbeiner, W., Gallup, M. & Basbaum, C. (2006). Wnt and Hedgehog are critical mediators of cigarette smoke-induced lung cancer. PLoS One 1, e93.
66. Narayan, S., Jaiswal, A.S., Kang, D., Srivastava, P., Das, G.M. & Gairola, C.G. (2004). Cigarette smoke condensate-induced transformation of normal human breast epithelial cells in vitro. Oncogene 23, 5880-5889. (Pubitemid 39093532)
67. Perocco, P., Paolini, M., Mazzullo, M., Biagi, G.L. & Cantelli-Forti, G. (1999). Beta-carotene as enhancer of cell transforming activity of powerful carcinogens and cigarette-smoke condensate on BALB/c 3T3 cells in vitro. Mutation Research 440, 83-90. (Pubitemid 29129529)
68. Rhim, J.S. & Huebner, R.J. (1973). In vitro transformation assay of major fractions of cigarette smoke condensate (CSC) in mammalian cell lines. Proceedings of the Society for Experimental Biology & Medicine 142, 1003-1007.
69. Schlage, W.T., Bulles, H., Friedrichs, D. & Kurkowsky, B. (1999). Two-stage transformation assay for cigarette smoke condensates using murine C3H-10T1/2 fibroblasts. Toxicology in Vitro 13, 823-828. (Pubitemid 29354218)
70. Zhou, H., Calaf, G.M. & Hei, T.K. (2003). Malignant transformation of human bronchial epithelial cells with the tobacco-specific nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone. International Journal of Cancer 106, 821-826. (Pubitemid 37071659)
71. Kim, J.B. (2005). Three-dimensional tissue culture models in cancer biology. Seminars in Cancer Biology 15, 365-377.
72. Friedrich, M.J. (2003). Studying cancer in 3 dimensions: 3-D models foster new insights into tumorigenesis. Journal of the American Medical Association 290, 1977-1979.
73. Guillouzo, A. (1998). Liver cell models in in vitro toxicology. Environmental Health Perspectives 106, Suppl. 2, 511-532.
74. Coussens, L.M. & Werb, Z. (2002). Inflammation and cancer. Nature, London 420, 860-867. (Pubitemid 36019639)
75. Lopez, J.I., Mouw, J.K. & Weaver, V.M. (2008). Biomechanical regulation of cell orientation and fate. Oncogene 27, 6981-6993.
76. Bissell, M.J., Radisky, D.C., Rizki, A., Weaver, V.M. & Petersen, O.W. (2002). The organizing principle: Microenvironmental influences in the normal and malignant breast. Differentiation 70, 537-546. (Pubitemid 36194318)
77. Seales, E.C., Belousova, M. & Singh, R.K. (2007). 3D tumourigenesis and angiogenesis assay models: Predicting better functional and preclinical end-points. Drug Discovery International May, 3-61.
78. Vargo-Gogola, T. & Rosen, J.M. (2007). Modelling breast cancer: One size does not fit all. Nature Reviews Cancer 7, 659-672. (Pubitemid 47327411)
79. Kleinman, H.K. & Martin, G.R. (2005). Matrigel: Basement membrane matrix with biological activity. Seminars in Cancer Biology 15, 378-386. (Pubitemid 41140305)
80. Walles, T., Weimer, M., Linke, K., Michaelis, J. & Mertsching, H. (2007). The potential of bioartificial tissues in oncology research and treatment. Onkologie 30, 388-394. (Pubitemid 47013378)
81. Kunz-Schughart, L.A., Freyer, J.P., Hofstaedter, F. & Ebner, R. (2004). The use of 3-D cultures for high-throughput screening: The multicellular spheroid model. Journal of Biomolecular Screening 9, 273-285.
82. Auerbach, R., Lewis, R., Shinners, B., Kubai, L. & Akhtar, N. (2003). Angiogenesis assays: A critical overview. Clinical Chemistry 49, 32-40. (Pubitemid 36078551)
83. Harper, J. & Moses, M.A. (2006). Molecular regulation of tumor angiogenesis: Mechanisms and therapeutic implications. In Experientia Supplementum, Vol. 96. Cancer: Cell Structures, Carcinogens and Genomic Instability (ed. L.P. Bignold), pp. 223-268. Basel, Switzerland: Birkhäuser Verlag.
84. Hasina, R. & Lingen, M.W. (2001). Angiogenesis in oral cancer. Journal of Dental Education 65, 1282-1290.
85. Folkman, J. (1995). Tumor angiogenesis. In The Molecular Basis of Cancer (ed. J. Mendelsohn, P.M. Howley, M.A. Israel & L.A. Liott), pp. 206-232. Philadelphia, PA, USA: W.B. Saunders.
86. Albini, A. & Benelli, R. (2007). The chemoinvasion assay: A method to assess tumor and endothelial cell invasion and its modulation. Nature Protocols 2, 504-511. (Pubitemid 47040014)
87. Goodwin, A.M. (2007). In vitro assays of angiogenesis for assessment of angiogenic and antiangiogenic agents. Microvascular Research 74, 172-183.
88. Kleinman, H.K. & Jacob, K. (1998). Invasion assays. In Current Protocols in Cell Biology (ed. J.S. Bonifacino, M. Dasso, J.B. Harford, J. Lippincott-Schwartz & K.M. Yamada), pp. 12.2.1-12.2.5. Hoboken, NJ, USA: John Wiley & Sons, Inc.
89. Woo, M.M., Salamanca, C.M., Minor, A. & Auersperg, N. (2007). An improved assay to quantitate the invasiveness of cells in modified Boyden chambers. In Vitro Cellular & Developmental Biology - Animal 43, 7-9. (Pubitemid 47087329)
90. Mousa, S. & Mousa, S.A. (2006). Cellular and molecular mechanisms of nicotine's pro-angiogenesis activity and its potential impact on cancer. Journal of Cellular Biochemistry 97, 1370-1378.
91. Zhang, Q., Tang, X., Zhang, Z.F., Velikina, R., Shi, S. & Le, A.D. (2007). Nicotine induces hypoxia-inducible factor-1alpha expression in human lung cancer cells via nicotinic acetylcholine receptor-mediated signaling pathways. Clinical Cancer Research 13, 4686-4694. (Pubitemid 47294774)
92. Martinez-Garcia, E., Irigoyen, M., Gonzalez-Moreno, O., Corrales, L., Teijeira, A., Salvo, E. & Rouzaut, A. (2010). Repetitive nicotine exposure leads to a more malignant and metastasis-prone phenotype of SCLC: A molecular insight into the importance of quitting smoking during treatment. Toxicological Sciences 116, 467-476.
93. Lawley, T.J. & Kubota, Y. (1989). Induction of morphologic differentiation of endothelial cells in culture. Journal of Investigative Dermatology 93, 59S-61S.
94. Nehls, V. & Drenckhahn, D. (1995). A novel, microcarrier-based in vitro assay for rapid and reliable quantification of three-dimensional cell migration and angiogenesis. Microvascular Research 50, 311-322.
95. Arnaoutova, I., George, J., Kleinman, H.K. & Benton, G. (2009). The endothelial cell tube formation assay on basement membrane turns 20: State of the science and the art. Angiogenesis 12, 267-274.
96. Nakatsu, M.N. & Hughes, C.C. (2008). An optimized three-dimensional in vitro model for the analysis of angiogenesis. Methods in Enzymology 443, 65-82.
97. Taraboletti, G. & Giavazzi, R. (2004). Modelling approaches for angiogenesis. European Journal of Cancer 40, 881-889. (Pubitemid 38519766)
98. Deshpande, A., Sicinski, P. & Hinds, P.W. (2005). Cyclins and cdks in development and cancer: A perspective. Oncogene 24, 2909-2915. (Pubitemid 40638099)
99. Merrick, K.A. & Fisher, R.P. (2010). Putting one step before the other: Distinct activation pathways for Cdk1 and Cdk2 bring order to the mammalian cell cycle. Cell Cycle 9, 706-714.
100. Morgan, D.O. (1997). Cyclin-dependent kinases: Engines, clocks, and microprocessors. Annual Review of Cell & Developmental Biology 13, 261-291.
101. Murray, A.W. (2004). Recycling the cell cycle: Cyclins revisited. Cell 116, 221-234.
102. Malumbres, M. & Barbacid, M. (2007). Cell cycle kinases in cancer. Current Opinions in Genetics & Development 17, 60-65. (Pubitemid 46109297)
103. Darzynkiewicz, Z., Juan, G. & Bedner, E. (1999). Determining cell cycle stages by flow cytometry. In Current Protocols in Cell Biology (ed. J.S. Bonifacino, M. Dasso, J.B. Harford, J. Lippincott-Schwartz & K.M. Yamada), Volume 2 Chapter 8, pp. 8.4.1-8.4.18. Hoboken, NJ, USA: John Wiley & Sons, Inc.
104. Pozarowski, P. & Darzynkiewicz, Z. (2004). Analysis of cell cycle by flow cytometry. Methods in Molecular Biology 281, 301-311.
105. Gasparri, F., Cappella, P. & Galvani, A. (2006). Multiparametric cell cycle analysis by automated microscopy. Journal of Biomolecular Screening 11, 586-598. (Pubitemid 44315956)
106. Darzynkiewicz, Z. (1992). Mammalian cell cycle analysis. In The Cell Cycle: A Practical Approach. (ed. P. Fantes & R. Brooks), pp. 45-68. Oxford, UK: Oxford University Press.
107. Gray, J.W., Dolbeare, F. & Pallavicini, M.G. (1990). Quantitative cell cycle analysis. In Flow Cytometry & Sorting (ed. M.R. Melamed, T. Lindmo & M.L. Mendelsohn), pp. 445-467. New York, NY, USA: Wiley-Liss.
108. Langenfeld, J., Lonardo, F., Kiyokawa, H., Passalaris, T., Ahn, M.J., Rusch, V. & Dmitrovsky, E. (1996). Inhibited transformation of immortalized human bronchial epithelial cells by retinoic acid is linked to cyclin E down-regulation. Oncogene 13, 1983-1990. (Pubitemid 26397458)
109. Ho, Y.S., Chen, C.H., Wang, Y.J., Pestell, R.G., Albanese, C., Chen, R.J., Chang, M.C., Jeng, J.H., Lin, S.Y., Liang, Y.C., Tseng, H., Lee, W.S., Lin, J.K., Chu, J.S., Chen, L.C., Lee, C.H., Tso, W.L., Lai, Y.C. & Wu, C.H. (2005). Tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1- butanone (NNK) induces cell proliferation in normal human bronchial epithelial cells through NFkappaB activation and cyclin D1 up-regulation. Toxicology & Applied Pharmacology 205, 133-148. (Pubitemid 40704648)
110. Kerr, J.F., Wyllie, A.H. & Currie, A.R. (1972). Apoptosis: A basic biological phenomenon with wide-ranging implications in tissue kinetics. British Journal of Cancer 26, 239-257.
111. Dasso, M. (2005). Cellular aging and death. In Current Protocols in Cell Biology (ed. J.S. Bonifacino, M. Dasso, J.B. Harford, J. Lippincott-Schwartz & K.M. Yamada), pp. 18.1.1-18.1.8. Hoboken, NJ, USA: John Wiley & Sons, Inc.
112. Raff, M. (1998). Cell suicide for beginners. Nature, London 396, 119-122.
113. Elmore, S. (2007). Apoptosis: A review of programmed cell death. Toxicologic Pathology 35, 495-516.
114. Saraste, A. & Pulkki, K. (2000). Morphologic and biochemical hallmarks of apoptosis. Cardiovascular Research 45, 528-537. (Pubitemid 30047119)
115. Rhyne, P.W., Scull, J.D., Stiles, L.M. & Eisinger, D.P. (2003). Analysis of apoptotic cells using Beadlyte suspension arrays. Biotechniques 35, 624-629. (Pubitemid 37108264)
116. Meso Scale Discovery (2009). MSD® Multiplex Apoptosis Panel: Phospho p53 (pSer15), Total p53, Cleaved PARP and Cleaved Caspase-3, 4pp. Gaithersburg, MD, USA: Meso Scale Discovery. Available at: www.meso-scale.com/ CatalogSystemWeb/Documents/Apoptosis-Panel.pdf (Accessed 19.05.11).
117. Chang, S.S., Jiang, W.W., Smith, I., Glazer, C., Sun, W.Y., Mithani, S. & Califano, J.A. (2010). Chronic cigarette smoke extract treatment selects for apoptotic dysfunction and mitochondrial mutations in minimally transformed oral keratinocytes. International Journal of Cancer 126, 19-27.
118. Mu, J. & Wei, L.X. (2002). Telomere and telomerase in oncology. Cell Research 12, 1-7. (Pubitemid 135708298)
119. Wai, L.K. (2004). Telomeres, telomerase, and tumorigenesis - a review. Medscape General Medicine 6, 19.
120. Deng, Y., Chan, S.S. & Chang, S. (2008). Telomere dysfunction and tumour suppression: The senescence connection. Nature Reviews Cancer 8, 450-458. (Pubitemid 351744962)
121. Lantuejoul, S., Salon, C., Soria, J.C. & Brambilla, E. (2007). Telomerase expression in lung preneoplasia and neoplasia. International Journal of Cancer 120, 1835-1841. (Pubitemid 46418357)
122. Shay, J.W. & Wright, W.E. (2007). Hallmarks of telomeres in ageing research. Journal of Pathology 211, 114-123. (Pubitemid 46195510)
123. Blasco, M.A. (2005). Telomeres and human disease: Ageing, cancer and beyond. Nature Reviews Genetics 6, 611-622.
124. Dunham, M.A., Neumann, A.A., Fasching, C.L. & Reddel, R.R. (2000). Telomere maintenance by recombination in human cells. Nature Genetics 26, 447-450.
125. Herbert, B.S., Shay, J.W. & Wright, W.E. (2003). Analysis of telomeres and telomerase. In Current Protocols in Cell Biology (ed. J.S. Bonifacino, M. Dasso, J.B. Harford, J. Lippincott-Schwartz & K.M. Yamada), pp. 18.6.1-18.6.20. Hoboken, NJ, USA: John Wiley & Sons, Inc.
126. Saldanha, S.N., Andrews, L.G. & Tollefsbol, T.O. (2003). Analysis of telomerase activity and detection of its catalytic subunit, hTERT. Analytical Biochemistry 315, 1-21. (Pubitemid 36379101)
127. Xiao, Y., Dane, K.Y., Uzawa, T., Csordas, A., Qian, J., Soh, H.T., Daugherty, P.S., Lagally, E.T., Heeger, A.J. & Plaxco, K.W. (2010). Detection of telomerase activity in high concentration of cell lysates using primer-modified gold nanoparticles. Journal of the American Chemical Society 132, 15,299-15,307.
128. Lin, K.W. & Yan, J. (2005). The telomere length dynamic and methods of its assessment. Journal of Cellular & Molecular Medicine 9, 977-989.
129. Hacia, J.G., Novotny, E.A., Mayer, R.A., Woski, S.A., Ashlock, M.A. & Collins, F.S. (1999). Design of modified oligodeoxyribonucleotide probes to detect telomere repeat sequences in FISH assays. Nucleic Acids Research 27, 4034-4039. (Pubitemid 29479030)
130. Perner, S., Bruderlein, S., Hasel, C., Waibel, I., Holdenried, A., Ciloglu, N., Chopurian, H., Nielsen, K.V., Plesch, A., Hogel, J. & Moller, P. (2003). Quantifying telomere lengths of human individual chromosome arms by centromere-calibrated fluorescence in situ hybridization and digital imaging. American Journal of Pathology 163, 1751-1756. (Pubitemid 37310006)
131. Ishikawa, F. (1998). FISH goes with the flow. Nature Biotechnology 16, 723-724.
132. Rufer, N., Brummendorf, T.H., Kolvraa, S., Bischoff, C., Christensen, K., Wadsworth, L., Schulzer, M. & Lansdorp, P.M. (1999). Telomere fluorescence measurements in granulocytes and T lymphocyte subsets point to a high turnover of hematopoietic stem cells and memory T cells in early childhood. Journal of Experimental Medicine 190, 157-167. (Pubitemid 29354909)
133. Canela, A., Vera, E., Klatt, P. & Blasco, M.A. (2007). High-throughput telomere length quantification by FISH and its application to human population studies. Proceedings of the National Academy of Sciences of the USA 104, 5300-5305. (Pubitemid 47175675)
134. Baird, D.M., Rowson, J., Wynford-Thomas, D. & Kipling, D. (2003). Extensive allelic variation and ultrashort telomeres in senescent human cells. Nature Genetics 33, 203-207. (Pubitemid 36177075)
135. Saldanha, S.N., Andrews, L.G. & Tollefsbol, T.O. (2003). Assessment of telomere length and factors that contribute to its stability. European Journal of Biochemistry 270, 389-403. (Pubitemid 36177306)
136. Canela, A., Klatt, P. & Blasco, M.A. (2007). Telomere length analysis. Methods in Molecular Biology 371, 45-72. (Pubitemid 350183417)
137. Ruch, R.J. (1994). The role of gap junctional intercellular communication in neoplasia. Annals of Clinical & Laboratory Science 24, 216-231.
138. Loewenstein, W.R. (1979). Junctional intercellular communication and the control of growth. Biochimica et Biophysica Acta 560, 1-65.
139. Bruzzone, R., White, T.W. & Paul, D.L. (1996). Connections with connexins: The molecular basis of direct intercellular signaling. Euopean Journal of Biochemistry 238, 1-27. (Pubitemid 26164180)
140. Trosko, J.E. & Chang, C.C. (2001). Role of stem cells and gap junctional intercellular communication in human carcinogenesis. Radiation Research 155, 175-180. (Pubitemid 33723535)
141. Janssen-Timmen, U., Traub, O., Dermietzel, R., Rabes, H.M. & Willecke, K. (1986). Reduced number of gap junctions in rat hepatocarcinomas detected by monoclonal antibody. Carcinogenesis 7, 1475-1482.
142. Loewenstein, W.R. & Rose, B. (1992). The cell-cell channel in the control of growth. Seminars in Cell Biology 3, 59-79.
143. McKarns, S.C., Bombick, D.W., Morton, M.J. & Doolittle, D.J. (2000).
144. Tai, M.H., Upham, B.L., Olson, L.K., Tsao, M.S., Reed, D.N., Jr & Trosko, J.E. (2007). Cigarette smoke components inhibited intercellular communication and differentiation in human pancreatic ductal epithelial cells. International Journal of Cancer 120, 1855-1862. (Pubitemid 46418360)
145. van der Zandt, P.T., de Feijter, A.W., Homan, E.C., Spaaij, C., de Haan, L.H., van Aelst, A.C. & Jongen, W.M. (1990). Effects of cigarette smoke condensate and 12-O-tetradecanoylphorbol-13-acetate on gap junction structure and function in cultured cells. Carcinogenesis 11, 883-888. (Pubitemid 20207337)
146. Upham, B.L., Blaha, L., Babica, P., Park, J.S., Sovadinova, I., Pudrith, C., Rummel, A.M., Weis, L.M., Sai, K., Tithof, P.K., Guzvic, M., Vondracek, J., Machala, M. & Trosko, J.E. (2008). Tumor promoting properties of a cigarette smoke prevalent polycyclic aromatic hydrocarbon as indicated by the inhibition of gap junctional intercellular communication via phosphatidylcholine-specific phospholipase C. Cancer Sciences 99, 696-705. (Pubitemid 351453829)
147. Cowles, C., Mally, A. & Chipman, J.K. (2007). Different mechanisms of modulation of gap junction communication by non-genotoxic carcinogens in rat liver in vivo. Toxicology 238, 49-59. (Pubitemid 47088048)
148. Cruciani, V., Rast, C., Durand, M.J., Nguyen-Ba, G. & Vasseur, P. (1997). Comparative effects of clofibrate and methyl clofenapate on morphological transformation and intercellular communication of Syrian hamster embryo cells. Carcino genesis 18, 701-706. (Pubitemid 28132456)
149. Husoy, T., Mikalsen, S.O. & Sanner, T. (1993). Effects of five phorbol esters on gap junctional intercellular communication, morphological transformation and epidermal growth factor binding in Syrian hamster embryo cells. Carcinogenesis 14, 73-77. (Pubitemid 23152746)
150. Mikalsen, S.O. (1993). Heterologous gap junctional intercellular communication in normal and morphologically transformed colonies of Syrian hamster embryo cells. Carcinogenesis 14, 2085-2090.
151. Katoh, F., Fitzgerald, D.J., Giroldi, L., Fujiki, H., Sugimura, T. & Yamasaki, H. (1990). Okadaic acid and phorbol esters: Comparative effects of these tumor promoters on cell transformation, intercellular communication and differentiation in vitro. Japanese Journal of Cancer Research 81, 590-597. (Pubitemid 20236574)
152. Katoh, F. & Yamasaki, H. (1991). Regulation of gap-junctional intercellular communication in transformation-sensitive and transformationresistant BALB/c 3T3 cell variants. Carcinogenesis 12, 1923-1926.
153. Yamasaki, H. (1995). Non-genotoxic mechanisms of carcinogenesis: Studies of cell transformation and gap junctional intercellular communication. Toxicology Letters 77, 55-61.
154. Kanno, Y. & Loewenstein, W.R. (1964). Inter cellular diffusion. Science, New York 143, 959-960.
155. el-Fouly, M.H., Trosko, J.E. & Chang, C.C. (1987). Scrape-loading and dye transfer. A rapid and simple technique to study gap junctional intercellular communication. Experimental Cell Research 168, 422-430. (Pubitemid 17012631)
156. Raptis, L.H., Brownell, H.L., Firth, K.L. & Mackenzie, L.W. (1994). A novel technique for the study of intercellular, junctional communication: Electroporation of adherent cells on a partly conductive slide. DNA Cell Biology 13, 963-975. (Pubitemid 24376828)
157. Chen, S. & Lee, L.P. (2010). Non-invasive microfluidic gap junction assay. Integrative Biology 2, 130-138.
158. Abbaci, M., Barberi-Heyob, M., Blondel, W., Guillemin, F. & Didelon, J. (2008). Advantages and limitations of commonly used methods to assay the molecular permeability of gap junctional intercellular communication. Biotechniques 45, 33-62.
159. McKarns, S.C. & Doolittle, D.J. (1991). A quantitative approach to assessing intercellular communication: Studies on cigarette smoke condensates. Toxicology & Applied Pharmacology 111, 58-68.
160. Machala, M., Svihalkova-Sindlerova, L., Pencikova, K., Krcmar, P., Topinka, J., Milcova, A., Novakova, Z., Kozubik, A. & Vondracek, J. (2008). Effects of methylated chrysenes on AhR-dependent and -independent toxic events in rat liver epithelial cells. Toxicology 247, 93-101.
161. Meckley, D.R., Hayes, J.R., Van Kampen, K.R., Ayres, P.H., Mosberg, A.T. & Swauger, J.E. (2004). Comparative study of smoke condensates from 1R4F cigarettes that burn tobacco versus ECLIPSE cigarettes that primarily heat tobacco in the SENCAR mouse dermal tumor promotion assay. Food & Chemical Toxicology 42, 851-863. (Pubitemid 38376353)
162. Blaha, L., Babica, P., Hilscherova, K. & Upham, B.L. (2010). Inhibition of gap-junctional intercellular communication and activation of mitogen-activated protein kinases by cyanobacterial extracts - indications of novel tumor-promoting cyanotoxins? Toxicon 55, 126-134.
163. Davis, A.P., King, B.L., Mockus, S., Murphy, C.G., Saraceni-Richards, C., Rosenstein, M., Wiegers, T. & Mattingly, C.J. (2010). The Comparative Toxicogenomics Database: Update 2011. Nucleic Acids Research 39, Suppl. 1, D1067-D1072.
164. Waters, M.D., Jackson, M. & Lea, I. (2010). Characterizing and predicting carcinogenicity and mode of action using conventional and toxicogenomics methods. Mutation Research 705, 184-200.
165. Rohrbeck, A., Salinas, G., Maaser, K., Linge, J., Salovaara, S., Corvi, R. & Borlak, J. (2010). Toxicogenomics applied to in vitro carcinogenicity testing with Balb/c 3T3 cells revealed a gene signature predictive of chemical carcinogens. Toxicological Sciences 118, 31-41.
166. European Commission (2008). Proposal for a Directive of the European Parliament and of the Council on the Protection of Animals Used for Scientific Purposes. Brussels, 5.11.2008, COM(2008) 543 final, 88pp. Brussels, Belgium: Commission of the European Communities. Available at: http://eur-lex.europa.eu/ LexUriServ/LexUriServ.do?uri=COM:2008:0543:FIN:EN:PDF (Accessed 19.05.11).
167. Anon. (1986). Council Directive 86/609/EEC of 24 November 1986 on the approximation of laws, regulations and administrative provisions of the Member States regarding the protection of animals used for experimental and other scientific purposes. Official Journal of the European Union L358, 18.12.1986, 1-28.
168. ECVAM (2006). Statement on the Scientific Validity of the In Vitro Micronucleus Test as an Alternative to the In Vitro Chromosome Aberration Assay for Genotoxicity Testing, 2pp. Ispra, Italy: European Commission, Joint Research Centre, Institute for Health and Consumer Protection, European Centre for the Validation of Alternative Methods. Available at: http://ecvam.jrc.it/ publication/ESAC25-statement-MNT-20061128-C.pdf (Accessed 19.05.11).
169. ESAC (2006). ECVAM Scientific Advisory Committee (ESAC) Peer Review, Retrospective Validation of the In Vitro Micronucleus Test, Summary and Conclusions of the Peer Review Panel, 10pp. Ispra, Italy: European Commission, Joint Research Centre, Institute for Health and Consumer Protection, European Centre for the Validation of Alternative Methods, Scientific Advisory Committee.
170. OECD (2010). OECD Guideline for the Testing of Chemicals. No. 487: In Vitro Mammalian Cell Micronucleus Test, 23pp. Paris, France: Organisation for Economic Co-operation and Development. Available at: http://titania.sourceoecd. org/vl=30196851/cl=17/nw=1/rpsv/cw/vhosts/oecdjournals/1607310x/v1n4/contp1-1. htm (Accessed 19.05.11).
171. Vanparys, P., Corvi, R., Aardema, M., Gribaldo, L., Hayashi, M., Hoffmann, S. & Schechtman, L. (2011). ECVAM prevalidation of three cell transformation assays. ALTEX 28, 56-59.
172. Cattaneo, M., Fontanella, E., Canton, C., Delia, D. & Biunno, I. (2005). SEL1L affects human pancreatic cancer cell cycle and invasiveness through modulation of PTEN and genes related to cell-matrix interactions. Neoplasia 7, 1030-1038.
173. Lo Muzio, L., Santarelli, A., Emanuelli, M., Pierella, F., Sartini, D., Staibano, S., Rubini, C. & De Rosa, G. (2006). Genetic analysis of oral squamous cell carcinoma by cDNA microarrays focused apoptotic pathway. International Journal of Immunopathology & Pharmacology 19, 675-682. (Pubitemid 44580540)
174. Zhao, S., Zhang, J., Zhang, X., Dong, X. & Sun, X. (2008). Arsenic trioxide induces different gene expression profiles of genes related to growth and apoptosis in glioma cells dependent on the p53 status. Molecular Biology Reports 35, 421-429.
175. Tweats, D.J., Scott, A.D., Westmoreland, C. & Carmichael, P.L. (2007). Determination of genetic toxicity and potential carcinogenicity in vitro -challenges post the Seventh Amendment to the European Cosmetics Directive. Mutagenesis 22, 5-13. (Pubitemid 46058637)
176. Phillips, J., Kluss, B., Richter, A. & Massey, E. (2005). Exposure of bronchial epithelial cells to whole cigarette smoke: Assessment of cellular responses. ATLA 33, 239-248. (Pubitemid 40956800)
177. Miyagawa, Y., Okita, H., Hiroyama, M., Sakamoto, R., Kobayashi, M., Nakajima, H., Katagiri, Y.U., Fujimoto, J., Hata, J.I., Umezawa, A. & Kiyokawa, N. (2011). A microfabricated scaffold induces the spheroid formation of human bone marrow-derived mesenchymal progenitor cells and promotes efficient adipogenic differentiation. Tissue Engineering. Part A 17, 513-521.
178. Donovan, D., Brown, N.J., Bishop, E.T. & Lewis, C.E. (2001). Comparison of three in vitro human 'angiogenesis' assays with capillaries formed in vivo. Angiogenesis 4, 113-121. (Pubitemid 34032697)
179. Staton, C.A., Stribbling, S.M., Tazzyman, S., Hughes, R., Brown, N.J. & Lewis, C.E. (2004). Current methods for assaying angiogenesis in vitro and in vivo. International Journal of Experimental Pathology 85, 233-248. (Pubitemid 39319155)
180. Yu, C.C., Woods, A.L. & Levison, D.A. (1992). The assessment of cellular proliferation by immunohistochemistry: A review of currently available methods and their applications. Histochemical Journal 24, 121-131.
181. Park, M.S. & Koff, A. (1998). Overview of the cell cycle. In Current Protocols in Cell Biology (ed. J.S. Bonifacino, M. Dasso, J.B. Harford, J. Lippincott-Schwartz & K.M. Yamada), pp. 8.1.1-8.1.9. Hoboken, NJ, USA: John Wiley & Sons, Inc.