Intercellular communication, tumor promotion and non-genotoxic carcinogenesis: Relationships based upon structural considerations

Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis

Volumn 381, Issue 2, 1997, Pages 171-188

  Rosenkranz, Margalit ^a   Rosenkranz, Herbert S ^a   Klopman, Gilles ^b  

^a UNIVERSITY OF PITTSBURGH   (United States)

^b CASE WESTERN RESERVE UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

1,3 PROPANEDIOL; CARCINOGEN; CHEMICAL COMPOUND; MUTAGENIC AGENT; PROPANOLAMINE DERIVATIVE;

ARTICLE; CARCINOGENESIS; CELL COMMUNICATION; METABOLIC INHIBITION; NONHUMAN; PRIORITY JOURNAL; RODENT; STRUCTURE ACTIVITY RELATION; TUMOR PROMOTION;

ANIMALS; CARCINOGENICITY TESTS; CARCINOGENS; CELL COMMUNICATION; CELL TRANSFORMATION, NEOPLASTIC; DATABASES, FACTUAL; DEPRESSION, CHEMICAL; HUMANS; MEMBRANE LIPIDS; MOLECULAR STRUCTURE; SOLUBILITY; STRUCTURE-ACTIVITY RELATIONSHIP;

RODENTIA;

EID: 0031589692     PISSN: 00275107     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0027-5107(97)00165-6     Document Type: Article

References (96)

1. [1] W.R. Loewenstein, Permeability of membrane junctions, Ann. New York Acad. Sci. 137 (1996) 441-472.
2. [2] L.P. Yotti, C.C. Chang, J.E. Trosko, Elimination of metabolic cooperation in Chinese hamster cells by a tumor promoter, Science 206 (1979) 1089-1091.
3. [3] A.W. Murray, D.J. Fitzgerald, Tumor promoters inhibit metabolic cooperation in co-cultures of epidermal and 3T3 cells, Biochem. Biophys. Res. Commun. 91 (1979) 395-401.
4. [4] J.E. Trosko, L.P. Yotti, B. Dawson, C.C. Chang, In vitro assay for tumor promoters, in: H.F. Stich, R.H.C. Tan (Eds.), Short-Term Tests for Chemical Carcinogens, Springer-Verlag, New York, 1980, pp. 420-427.
5. [5] S.H.H. Swierenga, H. Yamasaki, Performance of tests for cell transformation and gap-junction intercellular communication for detecting nongenotoxic carcinogenic activity, in: H. Vainio, P.N. Magee, D.B. McGregor, A.J. McMichael (Eds.), Mechanisms of Carcinogenesis in Risk Identification (Scientific Publication No. 116), International Agency for Research on Cancer, Lyon, 1992, pp. 165-193.
6. [6] M.J. Zeilmaker, H. Yamasaki, Inhibition of junctional intercellular communication as a possible short-term test to detect tumor-promoting agents: results with nine chemicals tested by dye transfer assay in Chinese hamster V79 cells, Cancer Res. 46 (1986) 6180-6186.
7. [7] J.E. Trosko, C.C. Chang, Nongenotoxic mechanisms in carcinogenesis: role of inhibited intercellular communication, in: R.W. Hoerger, F.D. Hoerger, (Eds.), Banbury Report 31: Carcinogen Risk Assessment: New Directions in Qualitative and Quantitative Aspects Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, 1988, pp. 139-174.
8. [8] I.V. Budunova, G.M. Williams, Cell culture assays for chemicals with tumor-promoting or tumor-inhibiting activity based on the modulation of intercellular communication, Cell Biol. Toxicol. 10 (1994) 71-116.
9. [9] S.Y. Oh, C.G. Grupen, A.W. Murray, Phorbol ester induced phosphorylation and down regulation of connexin 43 in WB cells, Biochim. Biophys. Acta 1094 (1991) 243-245.
10. [10] L.S. Musil, D.A. Goodenough, Gap junctional intercellular communication and the regulation of connexin expression and function, Curr. Opin. Cell Biol. 2 (1990) 875-880.
11. [11] J.E. Trosko, C.C. Chang, B.V. Madhukar, Oncogenes, tumor suppressor genes, and intercellular communication in the 'Oncogeny as Partially Blocked Ontogeny Hypothesis', in: New Frontiers Cancer Causation, Taylor and Francis, Washington, DC, 1993, pp. 181-197.
12. [12] R. Bruzzone, T.W. White, D.A. Goodenough, The cellular internet: on-line with connexins, BioEssays 18 (1996) 709-718.
13. [13] H. Yamasaki, Role of disrupted gap junctional intercellular communication in detection and characterization of carcinogens, Mutation Res. 365 (1996) 91-105.
14. [14] H. Yamasaki, M. Mesnil, Y. Omori, N. Mironov, V. Krutovskikh, Intercellular communication and carcinogenesis, Mutation Res. 333 (1995) 181-188.
15. [15] X. Guan, S. Wilson, K.K. Schlender, R.J. Ruch, Gap-junction disassembly and connexin 43 dephosphorylation induced by 18β-glycyrrhetinic acid, Mol. Carcinogen. 16 (1996) 157-164.
16. [16] L.A.M. Jansen, M. Mesnil, W.M.F. Jongen, Inhibition of gap junctional intercellular communication and delocalization of the cell adhesion molecule E-cadherin by tumor promoters, Carcinogenesis 17 (1996) 1527-1531.
17. [17] L. Jansen, M. Mesnil, J. Koeman, W. Jongen, Tumor promoters induce inhibition of gap junctional intercellular communication in mouse epidermal cells by affecting the localization of connexin43 and E-cadherin, Environ. Toxicol. Pharmacol. 1 (1996) 185-192.
18. [18] M.J. Sawey, M.H. Goldschmidt, B. Risek, N.B. Gilula, C.W. Lo, Perturbation in connexin 43 and connexin 26 gap-junction expression in mouse skin hyperplasia and neoplasia, Mol. Carcinogen. 17 (1996) 49-61.
19. [19] M. Liu, N. Sussman, G. Klopman, H.S. Rosenkranz, Estimation of the optimal data base size for structure-activity analyses: the Salmonella mutagenicity data base, Mutation Res. 358 (1996) 63-72.
20. [20] G. Klopman, Artificial intelligence approach to structure-activity studies. Computer automated structure evaluation of biological activity of organic molecules, J. Am. Chem. Soc. 106 (1984) 7315-7321.
21. [21] G. Klopman, MULTICASE 1. A hierarchical computer automated structure evaluation program, Quant. Struct. Act. Rel. 11 (1992) 176-184.
22. [22] G. Klopman, H.S. Rosenkranz, Prediction of carcinogenicity/mutagenicity using MULTICASE, Mutation Res. 305 (1994) 33-46.
23. [23] A.R. Cunningham, G. Klopman, H.S. Rosenkranz, A dichotomy in the lipophilicity of natural estrogens/xenoestrogens and phytoestrogens, Environ. Health Perspect. 105 (Suppl. 3) (1997) 665-668.
24. [24] V. Chankong, Y.Y. Haimes, H.S. Rosenkranz, J. Pet-Edwards, The Carcinogenicity Prediction and Battery Selection (CPBS) method: a Bayesian approach, Mutation Res. 153 (1985) 135-166.
25. [25] Y.P. Zhang, N. Sussman, O.T. Macina, H.S. Rosenkranz, G. Klopman, Prediction of the carcinogenicity of a second group of chemicals undergoing carcinogenicity testing, Environ. Health Perspect. 104 (Suppl. 5) (1996) 1045-1050.
26. [26] O.T. Macina, Y.P. Zhang, H.S. Rosenkranz, Improved predictivity of carcinogens: the use of a battery of SAR models, in: K.T. Kitchin (Ed.), Testing, Predicting and Interpreting Carcinogenicity, in press.
27. [27] H.S. Rosenkranz, G. Klopman, Structural evidence for a dichotomy in rodent carcinogenesis: involvement of genetic and cellular toxicity, Mutation Res. 303 (1993) 83-89.
28. [28] H.S. Rosenkranz, Y.P. Zhang, G. Klopman, Evidence that cell toxicity may contribute to the genotoxic response, Regul. Toxicol. Pharmacol. 19 (1994) 176-182.
29. [29] V. Dunkel, E. Zeiger, D. Brusick, E.G. McCoy, D. McGregor, K. Mortelmans, H.S. Rosenkranz, V.F. Simmon, Reproducibility of microbial mutagenicity assays. I. Tests with Salmonella typhimurium and Escherichia coli using a standard protocol, Environ. Mutagen. 6 (Suppl. 2) (1984) 1-251.
30. [30] V.C. Dunkel, E. Zeiger, D. Brusick, E. McCoy, D. McGregor, K. Mortelmans, H.S. Rosenkranz, V.F. Simmon, Reproducibility of microbial mutagenicity assays. II. Testing of carcinogens and noncarcinogens in Salmonella typhimurium and Escherichia coli, Environ. Mutagen. 7 (Suppl. 5) (1985) 1-248.
31. [31] K. Mortelmans, S. Haworth, T. Lawlor, W.T. Speck, B. Tainer, E. Zeiger, Salmonella mutagenicity tests. II. Results from the testing of 270 chemicals, Environ. Mutagen. 8 (1986) 1-119.
32. [32] E. Zeiger, Carcinogenicity of mutagens: predictive capability of the Salmonella mutagenesis assay for rodent carcinogenicity, Cancer Res. 47 (1987) 1287-1296.
33. [33] E. Zeiger, B. Anderson, S. Haworth, T. Lawlor, K. Mortelmans, W. Speck, Salmonella mutagenicity tests. III. Results from 255 chemicals, Environ. Mutagen. 9 (Suppl. 9) (1987) 1-109.
34. [34] E. Zeiger, B. Anderson, S. Haworth, T. Lawlor, K. Mortelmans, Salmonella mutagenicity tests. IV. Results from the testing of 300 chemicals, Environ. Mol. Mutagen. 11 (Suppl. 12) (1988) 1-157.
35. [35] H.S. Rosenkranz, G. Klopman, The structural basis of the mutagenicity of chemicals in Salmonella typhimurium: The National Toxicology Program data base, Mutation Res. 228 (1990) 51-80.
36. [36] E. Zeiger, J. Ashby, G. Bakale, K. Enslein, G. Klopman, H.S. Rosenkranz, Prediction of Salmonella mutagenicity, Mutagenesis 11 (1996) 471-484.
37. [37] J. Ashby, Fundamental structural alerts to potential carcinogenicity or non-carcinogenicity, Environ. Mutagen. 7 (1985) 919-921.
38. [38] J. Ashby, R.W. Tennant, Definitive relationships among chemical structure, carcinogenicity and mutagenicity for 301 chemicals tested by the U.S. NTP, Mutation Res. 257 (1991) 229-306.
39. [39] J. Ashby, D. Paton, The influence of chemical structure on the extent and sites of carcinogenesis for 522 rodent carcinogens and 52 different chemical carcinogen exposures, Mutation Res. 286 (1993) 3-74.
40. [40] H.S. Rosenkranz, G. Klopman, Evaluation of the ability of CASE, an artificial intelligence structure-activity relational system, to predict structural alerts for genotoxicity, Mutagenesis 5 (1990) 525-527.
41. [41] H.S. Rosenkranz, G. Klopman, Structural alerts to genotoxicity: the interaction of human and artificial intelligence, Mutagenesis 5 (1990) 333-361.
42. [42] J.E. Trosko, Challenge to the simple paradigm that 'carcinogens' are 'mutagens' and to the in vitro and in vivo assays used to test the paradigm, Mutation Res. 373 (1997) 245-249.
43. [43] L.S. Gold, C.B. Sawyer, R. Magaw, G.M. Backman, M. de Veciana, R. Levinson, N.K. Hooper, W.R. Havender, L. Bernstein, R. Peto, M.C. Pike, B.N. Ames, A carcinogenic potency database of the standardized results of animal bioassays, Environ. Health Perspect. 58 (1984) 9-319.
44. [44] L.S. Gold, M. de Veciana, G.M. Backman, R. Magaw, P. Lopipero, M. Smith, M. Blumenthal, R. Levinson, L. Bernstein, B.N. Ames, Chronological supplement to the Carcinogenic Potency Database: standardized results of animal bioassays published through December 1982, Environ. Health Perspect. 67 (1986) 161-200.
45. [45] L.S. Gold, T.H. Slone, G.M. Backman, R. Magaw, M. Da Costa, P. Lopipero, M. Blumenthal, B.N. Ames, Second chronological supplement to the carcinogenic potency database: standardized results of animal bioassays published through December 1984 and by the National Toxicology Program through May 1986, Environ. Health Perspect. 74 (1987) 237-329.
46. [46] L.S. Gold, T.H. Slone, G.M. Backman, S. Eisenberg, M. DaCosta, M. Wong, N.B. Manley, L. Rohrbach, B.N. Ames, Third chronological supplement to the Carcinogenic Potency Database: standardized results of animal bioassays published through December 1986 and by the National Toxicology Program through June 1987, Environ. Health Perspect. 84 (1990) 215-286.
47. [47] L.S. Gold, N.B. Manley, T.H. Slone, G.B. Garfinkel, L. Rohrbach, B.N. Ames, The fifth plot of the Carcinogenic Potency Database: Results of animal bioassays published in the general literature through 1988 and by the National Toxicology Program through 1989, Environ. Health Perspect. 100 (1993) 65-135.
48. [48] H.S. Rosenkranz, Y.P. Zhang, G. Klopman, Risk identification using structural concepts: the potential carcinogenicity of praziquantel, Regulatory Toxicol. Pharmacol. 22 (1995) 152-161.
49. [49] J. Ashby, R.W. Tennant, Prediction of rodent carcinogenicity for 44 chemicals: results, Mutagenesis 9 (1994) 7-15.
50. [50] H.S. Rosenkranz, G. Klopman, Structural basis of carcinogenicity in rodents of genotoxicants and non-genotoxicants, Mutation Res. 228 (1990) 105-124.
51. [51] E.J. Matthews, J.W. Spalding, R.W. Tennant, Transformation of BALB/C-3T3 cells. V. Transformation responses of 166 chemicals compared with mutagenicity in Salmonella and carcinogenicity in rodent bioassay, Environ. Health Perspect. 101 (Suppl. 2) (1993) 347-482.
52. [52] G. Klopman, D. Pichelintsev, M. Frierson, S. Pennisi, K. Renskers, M. Dickens, Multiple computer automated structure evaluation methodology as an alternative to in vivo eye irritation testing, ATLA 21 (1993) 14-27.
53. [53] M. Ghanooni, D.R. Mattison, Y.P. Zhang, O.T. Macina, H.S. Rosenkranz, G. Klopman, Structural determinants associated with risk of human developmental toxicity, Am. J. Obstet. Gynecol. 176 (1997) 799-806.
54. [54] U. Rannug, M. Sjogren, A. Rannug, M. Gillner, R. Toftgard, J.-A. Gustafsson, H. Rosenkranz, G. Klopman, Use of artificial intelligence in structure-affinity correlations of 2,3,7,8-tetrachlorodibenzo-P-dioxin (TCDD) receptor ligands, Carcinogenesis 12 (1991) 2007-2016.
55. [55] E. ter Haar, H.S. Rosenkranz, E. Hamel, B.W. Day, Computational and molecular modeling evaluation of the structural basis for tubulin polymerization inhibition by colchicine site agents, Bioorganic Med. Chem. 4 (1996) 1659-1671.
56. [56] J.A. Swenberg, B. Short, S. Borghoff, J. Strasser, M. Charbonneau, The comparative pathobiology of α2μ-globulin nephropathy, Toxicol. Appl. Pharmacol. 97 (1989) 35-46.
57. [57] B. Rosner, Fundamentals of Biostatistics, 4th ed., Wadsworth Publishing Co., Belmont, CA, 1995.
58. [58] G. Klopman, S. Wang, A Computer Automated Structure Evaluation (CASE) approach to calculation of partition coefficient, J. Computat. Chem. 12 (1991) 1025-1032.
59. [59] G. Klopman, S. Wang, D.M. Balthasar, Estimation of aqueous solubility of organic molecules by the group contribution approach. Application to the study of biodegradation, J. Chem. Inf. Comp. Sci. 32 (1992) 474-482.
60. [60] J.J. Houser, G. Klopman, A new tool for the rapid estimation of charge distribution, J. Computat. Chem. 9 (1988) 893-904.
61. [61] J.J. Houser, G. Klopman, The rapid estimation of charge distribution. II. Heteroatoms, J. Computat. Chem. 13 (1992) 990-996.
62. [62] R.G. Pearson, Absolute electronegativity and hardness correlated with molecular orbital theory, Proc. Natl. Acad. Sci. USA 83 (1986) 8440-8441.
63. [63] G. Klopman, H.S. Rosenkranz, Structure-activity relations: maximizing the usefulness of mutagenicity and carcinogenicity data bases, Environ. Health Perspect. 96 (1991) 67-75.
64. [64] H.S. Rosenkranz, N. Takihi, G. Klopman, Structure activity-based predictive toxicology: an efficient and economical method for generating non-congeneric data bases, Mutagenesis 6 (1991) 391-394.
65. [65] H.S. Rosenkranz, A. Cunningham, G. Klopman, Identification of a 2-D geometric descriptor associated with non-genotoxic carcinogens and some estrogens and antiestrogens, Mutagenesis 11 (1996) 95-100.
66. [66] J.A. Miller, E.G. Miller, Ultimate chemical carcinogens as reactive mutagenic electrophiles, in: H.H. Hiatt, J.D. Watson, J.A. Winsten (Eds.), Origins of Human Cancer, Cold Spring Harbor Laboratory, Cold Spring Harbor, 1977, pp. 605-627.
67. [67] M.R. Na, S.K. Koo, D.Y. Kim, D.S. Punk, S.K. Phee, K.W. Kang, C. O. Joe, In vitro inhibition of gap junctional intercellular communication by chemical carcinogens, Toxicology 98 (1995) 199-206.
68. [68] C.J. Fitzer, C.A. O'Brian, J.G. Guillem, I.B. Weinstein, The regulation of protein kinase C by chenodeoxycholate, deoxycholate and several structurally related bile acids, Carcinogenesis 8 (1987) 217-220.
69. [69] P.J. Parker, L. Coussens, N. Totty, L. Rhee, S. Young, E. Chen, S. Stabel, M.D. Waterfield, A. Ullrich, The complete primary structure of protein kinase C - the major phorbol ester receptor, Science 233 (1986) 853-866.
70. [70] P.M. Blumberg, Protein kinase C as the receptor for the phorbol ester tumor promoters: Sixth Rhoads Memorial Award Lecture, Cancer Res. 48 (1988) 1-8.
71. [71] S. Wang, M.G. Kazanietz, P.M. Blumberg, V.E. Marquez, G.W.A. Milne, Molecular modeling and site-directed mutagenesis studies of a phorbol ester-binding site in protein kinase C, J. Med. Chem. 39 (1996) 2541-2553.
72. [72] P.E. Driedger, P.M. Blumberg, Specific binding of phorbol ester tumor promoters, Proc. Natl. Acad. Sci. USA 77 (1980) 567-571.
73. [73] H.S. Rosenkranz, G. Klopman, Structural relationships between mutagenicity, maximum tolerated dose, and carcinogenicity in rodents, Environ. Mol. Mutagen. 21 (1993) 193-206.
74. [74] M. Liu, N. Sussman, G. Klopman, H.S. Rosenkranz, Structure-activity and mechanistic relationships: the effects of chemical overlap on structural overlap in data bases of varying size and composition, Mutation Res. 372 (1996) 79-85.
75. [75] R. Montesano, T.J. Slaga, Initiation and promotion in carcinogenesis: an appraisal, Cancer Surveys 2 (1983) 613-621.
76. [76] H.C. Pilot, T. Goldsworthy, H.A. Campbell, A. Poland, Quantitative evaluation of the promotion by 2,3,7,8-tetrachlorodibenzo-p-dioxin of hepatocarcinogenesis from diethylnitrosamine, Cancer Res. 40 (1980) 3616-3620.
77. [77] L.H.J. De Haan, S. Halfwerk, S.E.L. Hovens, B. De Roos, J.H. Koeman, A. Brouwer, Inhibition of intercellular communication and induction of ethoxyresorufm-O-deethylase activity by polychlorobiphenyls, -dibenzo-p-dioxins and -dibenzo-furans in mouse hep1ClC7 cells, Environ. Toxicol. Pharmacol. 1 (1996) 27-37.
78. [78] A. Poland, D. Palen, E. Glover, Tumour promotion by TCDD in skin of HSR/J hairless mice, Nature 300 (1982) 271-273.
79. [79] R. Schulte-Hermann, I. Timmermann-Trosiener, J. Schuppler, Promotion of spontaneous preneoplastic cells in rat liver as a possible explanation of tumor production by nonmutagenic compounds, Cancer Res. 43 (1983) 839-844.
80. [80] M.A. Watson, T.R. Devereux, D.E. Marlarkey, M.W. Anderson, R.R. Maronpot, H-ras oncogene mutation spectra in B6C3F1 and C57BL/6 mouse liver tumors provide evidence for TCDD promotion of spontaneous and vinyl carbamate-initiated liver cells, Carcinogenesis 16 (1995) 1705-1710.
81. [81] P.A. Baeuerle, T. Henkel, Function and activation of NF-kappa B in the immune system, Annu. Rev. Immunol. 12 (1994) 141-179.
82. [82] P. Hainaut, J.D. Milner, Redox modulation of p53 conformation and sequence specific DNA binding in vitro, Cancer Res. 53 (1993) 4468-4473.
83. [83] P. Angel, M. Karin, The role of Jun, Fos and the AP-1 complex in cell-proliferation and transformation, Biochim. Biophys. Acta 1072 (1991) 129-157.
84. [84] Y. Devany, R.A. Gottlieb, T. Smeal, M. Karin, The mammalian ultraviolet response is triggered by activation of Src tyrosine kinases, Cell 71 (1992) 1081-1091.
85. [85] J.E. Trosko, C.-C. Chang, M. Netzloff, The role of inhibited cell-cell communication in teratogenesis, Teratog. Carcinog. Mutag. 2 (1982) 31-45.
86. [86] J.E. Trosko, C. Jone, C.C. Chang, Inhibition of gap-junctional-mediated intercellular communication, in vitro, by aldrin, dieldrin, and toxaphene: a possible cellular mechanism for their tumor promoting and neurotoxic effects, Mol. Toxicol. 1 (1987) 83-93.
87. [87] Y.X. Ye, D. Bombick, K. Hirst, G. Zhang, C.C. Chang, J.E. Trosko, T. Akara, The modulation of gap junctional communication by gossypol in various mammalian cell lines in vitro, Fund. Appl. Toxicol. 14 (1990) 817-832.
88. [88] V. Kinzel, G. Kreibich, E. Hecker, R. Süss, Stimulation of choline incorporation in cell cultures by phorbol derivatives and its correlation with their irritant and tumor-promoting activity, Cancer Res. 39 (1979) 2743-2750.
89. [89] S.M. Fischer, J.K. Baldwin, D.W. Jasheway, K.E. Patrick, O.S. Cameron, Phorbol ester induction of 8-lipoxygenase in inbred SENCAR (SSIN) but not C57BL/6J mice correlated with hyperplasia, edema, and oxidant generation but not ornithine decarboxylase induction, Cancer Res. 48 (1988) 658-664.
90. [90] M. Gschwendt, W. Kittstein, G. Fürstenberger, F. Marks, The mouse ear edema: a quantitatively evaluable assay for tumor promoting compounds and for inhibitors of tumor promotion, Cancer Lett. 25 (1984) 177-185.
91. [91] B. Sorg, R. Schmidt, S. Pečar, M. Schara, E. Hecker, Spin-labeled phorbol esters and their interactions with cellular membranes. III. Skin irritant and tumor-promoting activities of spin-labeled phorbol-12, 13-diesters and relationships to their particular structures, Carcinogenesis 9 (1988) 1829-1834.
92. [92] B.L. Upham, L.M. Weis, A.M. Rummel, S.J. Masten, J.E. Trosko, The effects of anthracene and methylated anthracenes on gap junctional intercellular communication in rat liver epithelial cells, Fund. Appl. Toxicol. 34 (1996) 260-264.
93. [93] L.M. Weis, B.L. Upham, A.M. Rummel, S.J. Masten, J.E. Trosko, Determining a correlation between elements of polycyclic aromatic hydrocarbons and inhibition of gap junction intercellular communication, Toxicologist 36 (1997) 59.
94. [94] C.F. Aylsworth, J.E. Trosko, C.W. Welsch, Influence of lipids on gap-junction-mediated intercellular communication between Chinese hamster cells in vitro, Cancer Res. 46 (1986) 4527-4533.
95. [95] P.A. Wender, K.F. Koehler, N.A. Sharkey, M.L. Dell'Aquila, P.M. Blumberg, Analysis of the phorbol ester pharmacophore on protein kinase C as a guide to the rational design of new classes of analogs, Proc. Natl. Acad. Sci. USA 83 (1986) 4214-4218.
96. [96] H. Nakamura, Y. Kishi, M.A. Pajares, R.R. Rando, Structural basis of protein kinase C activation by tumor promoters, Proc. Natl. Acad. Sci. USA 86 (1989) 9672-9676.