A Common Structural Pattern among Many Biologically Active Compounds of Both Natural and Synthetic Origin — A Novel Approach to the Design of Antineoplastic Agents

  • C. C. Cheng
Conference paper


A tricyclic chemical structural pattern, consisting of a phenyl ring attached to the 2-position of a naphthalene nucleus, or composed of various heterocyclic units with similar molecular structural arrangements, is observed among a large number of biologically and pharmacologically active compounds. Possible relationships between this structural pattern and certain essential biomolecules are discussed. The pattern per se is not sufficient for attaining biological activity. It is believed that with proper substituents attached to specific positions of both ring units, compounds with desired biological activity could be rationally designed.


Estrogen Anthracene Quinoline Benz Carbazole 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    a) Schneider W and Schroeder K, Aceto-papaverin und Coralyn (Hexadehydro coralydin). Ber. 53: 1459–1469, 1920;Google Scholar
  2. (b).
    Zee-Cheng KY and Cheng CC, Practical preparation of coralyne chloride. J. Pharm. Sci. 61: 969–971, 1972; Interaction between DNA and coralyne acetosulfate, an antileukemic compound. ibid 62: 1572–1573, 1973.Google Scholar
  3. 2.
    a) Bachmann WE and Chemerda JM, The synthesis of 9,10-dimethyl-1,2-benzanthreacene, 9,10-diethyl-1,2-benzanthracene and 5,9,10-trimethyl-1,2-benzanthracene. J. Am. Chem. Soc. 60: 1023–1026, 1938;CrossRefGoogle Scholar
  4. (b).
    Pullman A and Pullman B, Electronic structure and carcinogenic activity of aromatic molecules. New developments. Adv. Cancer Res. 3: 117–169, 1955.PubMedCrossRefGoogle Scholar
  5. 3.
    a) Wall ME, Wani MC and Taylor HL, Plant antitumor agents 27. Isolation, structure, and structure-activity relationships of alkaloids from Fagara macrophylla. J. Nat. Prod. 50: 1095 1099, 1987;Google Scholar
  6. (b).
    Zee-Cheng KY and Cheng CC, Synthesis of 5,6-dihydro-6-methoxynitidine and a practical preparation of nitidine chloride. J. Heterocycl. Chem. 10: 85–88, 1973.CrossRefGoogle Scholar
  7. 4.
    a) Dunlap CE and Warren S, The carcinogenic activity of some new derivatives of aromatic hydrocarbons. I. Compounds related to chrysene. Cancer Res. 3: 606–607, 1943; (b) Amin S, Huie K, Melikian AA, Leszczynska JM and Hecht SS, Comparative metabolic activation in mouse skin of the weak carcinogen 6-methylchrysene and the strong carcinogen 5-methylchrysene. Cancer Res. 45: 6406–6412, 1985.Google Scholar
  8. 5.
    Cheng CC, Engle RR, Hudson JR, Ing RB, Wood HB, Yan SJ and Zee-Cheng RKY, Absence of mutagenicity of coralyne and related antileukemic agents: structural comparison with the potent carcinogen 7,12-dimethylbenz[alanthracene. J. Pharm. Sci. 66: 1781–1783, 1977.PubMedCrossRefGoogle Scholar
  9. 6.
    US Department of Health and Human Services, Survey of compounds which have been tested for carcinogenic activity. Washington, DC, 1–16, 1951–1986.Google Scholar
  10. 7.
    Berger J, Sternbach LH, Isolation of antibiotic X-465A and its identification with chartreusin. J. Am. Chem. Soc. 80: 1636–1638, 1958.CrossRefGoogle Scholar
  11. 8.
    Simonitsch E, Eisenhuth W, Stamm OA and Schmidt H, Über die Struktur des chartreusins. I and II. Heiv. Chem. Acta, 47: 1459–1484, 1964.CrossRefGoogle Scholar
  12. 9.
    Beisler JA, Chartreusin, a glycosidic antitumor antibiotic from Streptomyces. Prog. Med. Chem. 19: 247–268, 1982.CrossRefGoogle Scholar
  13. 10.
    Konishi M, Sugawara K, Kofu F, Nishiyama Y, Tomita K, Miyaki T and Kawaguchi H, Elsamicins, new antitumor antibiotics related to chartreusin I. Production, isolation, characterization and antitumor activity. J. Antibiot. 39: 784–791, 1986.PubMedCrossRefGoogle Scholar
  14. 11.
    Sagawara K, Tsunakawa M, Konishi M, Kawaguchi H, Krishnan B, He CH and Clardy J, Elsamicins A and B, new antitumor antibiotics related to chartreusin. 2. Structures of elsamicins A and B. J. Org . Chem. 52: 996–1101, 1987.CrossRefGoogle Scholar
  15. 12.
    Elespuru RK and Gonda SK, Activation of antitumor agent gilvocarcins by visible light. Science, 223: 69–71, 1983.CrossRefGoogle Scholar
  16. 13.
    Takahashi K, Yoshida M, Tornita F and Shirahata K, Gilvocarcins, new antitumor antibiotics 2. Structural elucidation. J. Antibiot. 34: 271–275, 1981.PubMedCrossRefGoogle Scholar
  17. 14.
    Morimoto M, Okubo S, Tornita F and Marumo H, Gilvocarcins, new antibiotics 3. Antitumor activity. J. Antibiot. 34: 701–707, 1981.PubMedCrossRefGoogle Scholar
  18. 15.
    Sehgal SN, Czerkawski H, Kudelski A, Pandev K, Saucier R and Vezina C, Ravidomycin (AY-25,545), a new antitumor antibiotic. J. Antibiot. 36: 355–361, 1983.PubMedCrossRefGoogle Scholar
  19. 16.
    Rakhit S, Eng C, Baker H and Singh K, Chemical modification of ravidomycin and evaluation of biological activities of its derivatives. J. Antibiot. 36: 1490–1494, 1983.PubMedCrossRefGoogle Scholar
  20. 17.
    a) Okami Y, Antibiotics from marine microorganisms with reference to plasmid involvement. J. Nat. Prod. 42: 583–595, 1979;PubMedCrossRefGoogle Scholar
  21. (b).
    Imamura N, Kakinuma K, Ikekawa N, Tanaka H and Omura S, Biosynthesis of vineomycins Al and B2. J. Antibiot. 35: 602–608, 1982.PubMedCrossRefGoogle Scholar
  22. 18.
    a) Hayakawa Y, Iwakiri T, Imamura L, Seto H and ()take N, Studies on the isotetraceneone antibiotics. I. Capomycin, a new antitumor antibiotic. J. Antibiot. 38: 957–959, 1985; (b) Hayakawa Y, Furahata K, Seto H and ()take N,The structure of a new isotetracenone antibiotic, capomycin. Tetrahedron Lett. 26: 3471–3474, 1985.CrossRefGoogle Scholar
  23. 19.
    Sezaki M, Kondo S, Maeda K, Umezawa H and Ohno M, The structure of aquaymycin. Tetrahedron Lett. 26: 5171–5190, 1970.Google Scholar
  24. 20.
    Ohta K, Okazaki H and Kishi T, The absolute configuration of P-1894B (vineomycin A1), apotent prolyl hydroxylase inhibitor. Chem. Pharm. Bull. 30: 762–765, 1982.CrossRefGoogle Scholar
  25. 21.
    Trie H, Mizuno Y, Kouno I, Nagasawa T, Tani Y, Yamada H, Taga T and Osagi K, Structures of new antibiotic substances, sakyomicin A, B, C, and D; X-ray crystal and molecular structure of sakyomicin A. J. Chem. Soc. Chem. Commun. 174–175, 1983.Google Scholar
  26. 22.
    Hayakawa Y, Iwakiri T, Imamura K, Seto H and ()take N, Studies on the isotetracenone antibiotics II. Kerriamycins A, B and C, new antitumor antibiotics. J. Antibiot. 38: 960–963, 1985.PubMedCrossRefGoogle Scholar
  27. 23.
    Uchida T, Imota M, Watanabe Y, Miura K, Dobashi T, Matsuda N, Sawa T, Naganawa H, Hamada M, Takeuchi T and Umezawa H, Saquayamycins, new aquaymaycin-group antibiotics. J.Antibiot. 38: 1171–1181, 1985.PubMedCrossRefGoogle Scholar
  28. 24.
    Drantz H, Zähner H, Rohr J and Zeeck A, Metabolic products of microorganisms. 234. Urdamycins, new angucycline antibiotics from Streptomyces fradiae I. Isolation, characterization and biological properties. J. Antibiot. 39: 1657–1669, 1986.CrossRefGoogle Scholar
  29. 25.
    a) Kuntsmann MP and Mitscher LA, The structural characterization of tetrangomycin and tetrangulol. J. Org . Chem. 31: 2920–2925, 1966;Google Scholar
  30. (b).
    Brown PM and Thomson RH, Naturally occurring quinones, Part XXVI. A synthesis of tetrangulol (1,8-dihydroxy-3-methylbenz [al anthracene-7,12-quinone). J. Chem. Soc. Perkin. Trans. 1: 997–1000, 1976.CrossRefGoogle Scholar
  31. 26.
    Liu WC, Parker WL, Slusarchyk DS, Greenwood GL, Graham SF and Meyers E, Isolation, characterization, and structure of rabelomycin, a new antibiotic. J. Antibiot. 23: 437–441, 1970.PubMedCrossRefGoogle Scholar
  32. 27.
    Rasmussen RR, Nuss ME, Scherr MH, Mueller SL, McAlpine JB and Mitscher LA, Benzanthrins A and B, a new class of quinone antibiotics II. Isolation, elucidation of structure and potential antitumor activity. J. Antibiot. 39: 1515–1526, 1986.PubMedCrossRefGoogle Scholar
  33. 28.
    Rickards RW and Wu JP, Fujianmycins A and B, new benz[a]anthraquinone antibiotics from a Streptomyces species. J. Antibiot. 38: 513–515, 1985.PubMedCrossRefGoogle Scholar
  34. 29.
    Wilton JH, Cheney DC, Hokanson GC, French JC, He CH and Clardy J, A new dihydrobenz[a]anthraquinone antitumor antibiotic (PD-116740). J. Org . Chem. 50: 3936–3940, 1985.CrossRefGoogle Scholar
  35. 30.
    a) Rao KV, Biemann K and Woodward RB, The structure of streptonigrin. J. Am. Chem. Soc. 85: 2532–2533, 1963;CrossRefGoogle Scholar
  36. (b).
    Rivers SL, Whittington RM and Medrek TJ, Methyl ester of streptonigrin (NSC-45384) in treatment of malignant lymphoma. Cancer Chemother. Rep. 46: 17–21, 1965; 1965.Google Scholar
  37. 31.
    Chiu YYH and Lipscomb WN, Molecular and crystal structure of streptonigrin. J. Am. Chem. Soc. 97: 2525–2530, 1975.PubMedCrossRefGoogle Scholar
  38. 32.
    a) Liao TK, Nyberg WH and Cheng CC, Synthetic studies of the antitumor antibiotic streptonigrin. I. Synthesis of the A-B ring portion of streptonigrin. J. Heterocycl. Chem. 13: 1063–1065, 1976;CrossRefGoogle Scholar
  39. (b).
    Wittek PJ, Liao TK and Cheng CC, Synthetic studies of the antitumor antibiotic streptonigrin. 3. Synthesis of the C-D ring of streptonigrin by an unsymmetrical Ullmann reaction. J. Org . Chem. 44: 870–872, 1979.Google Scholar
  40. 33.
    Balitz DM, Bush JA, Brandner WT, Doyle TW, O’Herron FA, Isolation of levendamycin. A new antibiotic from Streptomyces lavendulae. J. Antibiot. 35: 259–265, 1982.CrossRefGoogle Scholar
  41. 34.
    Dexter DL, Hesson DP, Ardecky RJ, Rao GV, Tippett DL, Dusak BA, Paull KD, Plowman J, DeLarco BM, Narayanan VL and Farbes M, Activity of a novel 4-quinolinecarboxylic acid, NSC-368390 [6-Fluoro-2-(2’-fluoro-1,1’-biphenyl-4-yl)-3-methyl-4-quinolinecarboxylic acid sodium salt] against experimental tumors. Cancer Res. 45: 5563–5568, 1985.PubMedGoogle Scholar
  42. 35.
    Chen SF, Ruben RL and Dexter DL, Mechanism of action of the novel anticancer agent 6-fluoro-2-(2’-fluoro-1,1’-biphenyl-4-yl)-3-methyl-4-quinolinecarboxylic acid sodium salt (NSC 368390): Inhibition of de novo pyrimidine nucleotide biosynthesis. Cancer Res. 46: 5014–5019, 1986.PubMedGoogle Scholar
  43. 36.
    a) Campbell KN, Morris RC and Adams R, The structure of gossypol. I. J. Am. Chem. Soc. 59: 1723–1728, 1937;CrossRefGoogle Scholar
  44. (b).
    Adams R, Geissman TA and Edwards JD, Gossypol, a pigment of cottonseed. Chem. Rev. 60: 555–631, 1960.PubMedCrossRefGoogle Scholar
  45. 37.
    Lee CYG, Moon YS, Yuan JH and Chen AF, Enzyme inactivation and inhibition by gossypol. Mol. Cell. Biochem. 47: 65–70, 1982.PubMedCrossRefGoogle Scholar
  46. 38.
    Rosenberg LJ, Adlakha RC, Dasai DM and Rao PN, Inhibition of DNA polymerase a by gossypol. Biochim. Biophys. Acta 866: 258–267, 1986.PubMedCrossRefGoogle Scholar
  47. 39.
    a) Goodwin S, Smith AF and Homing EC, Alkaloids of Ochrosia elliptica Labill. J. Am. Chem. Soc. 81: 1903–1908, 1959;CrossRefGoogle Scholar
  48. (b).
    Svoboda GH, Poore GA and Montfort ML, Alkaloids of Ochrosia maculata Jacq. (Ochrosia borbonica Gmel.). J. Pharm. Sci. 57: 1720–1725, 1968.PubMedCrossRefGoogle Scholar
  49. 40.
    Lesca P, Lecointe P, Paoletti C and Mansuy D, Ellipticines as potent inhibitors of drug metabolism. Protective effect against chemical mutagenesis and carcinogenesis. Biochimie 60: 1011–1018, 1978.CrossRefGoogle Scholar
  50. 41.
    Ducrocq C, Bisagni É, Rivalle C and Lhosta JM, Synthesis of 10-substituted 5H-pyrido [3’,4’:4,5]pyrrolo[2,3-g]isoquinolines. J. Chem. Soc. Perkin. Trans. I: 142–145, 1979.CrossRefGoogle Scholar
  51. 42.
    a) Wall ME, Wani MC, Cook CE, Palmer KH, McPhail AT and Sim GA, Plant antitumor agents. I. The isolation and structure of camptothecin, a novel alkaloidal leukemia and tumor inhibitor from Camptotheca acuminata. J. Am. Chem. Soc. 88: 3888–3890, 1966;Google Scholar
  52. (b).
    Perdue RE, Wall ME, Hartwell JL and Abbott BJ, Comparison of the activity of crude Campotheca acuminata ethanolic extracts against lymphoid leukemia L-1210. Lloydia 31: 229–236, 1968;Google Scholar
  53. (c).
    Hutchinson CR, Camptothecin: Chemistry biogenesis and medicinal chemistry. Tetrahedron 37: 1047–1065, 1981.CrossRefGoogle Scholar
  54. 43.
    Kessel D, Bosmann HB and Lohr K, Camptothecin effects on DNA synthesis in murine leukemia cells. Biochim. Biophys. Acta. 269: 210–216, 1972.PubMedCrossRefGoogle Scholar
  55. 44.
    a) Svoboda GH, Alkaloids of Acronychia baueri (Bauerrella anstraliana). II. Extraction of the alkaloids and studies of structure-activity relationships. Lloydia 29: 206–224, 1966;Google Scholar
  56. (b).
    Brannon DR, Horton DR and Svoboda GH, Microbial hydroxylation of acronycine. J. Med. Chem. 17: 653–654, 1974.PubMedCrossRefGoogle Scholar
  57. 45.
    Funayama S and Cordell GA, Chemistry of acronycine, XI. Rearrangement of dihydronoracronycine to dihydroisonoracronycine. Mechanistic studies. J. Nat. Prod. 48: 938–943, 1985.PubMedCrossRefGoogle Scholar
  58. 46.
    Cordell GA, Personal Communication, December 3, 1985.Google Scholar
  59. 47.
    Garzon K and Svoboda GH, Acridone alkaloids: Experimental antitumor activity of acronycine. The Alkaloids 21: 1–28, 1983.Google Scholar
  60. 48.
    a) Harborne JB, Mabry TJ and Malory H (eds), The Flavonoids, Academy Press, New York, NY 1975;Google Scholar
  61. (b).
    Harbome JB and Malory TJ (eds), The Flavonoids. Advances in Research, Chapman and Hall, London, 1982.Google Scholar
  62. 49.
    a) Haysteen B, Flavonoids, a class of natural products of high pharmacological potency. Biochem. Pharmacol. 32: 1141–1148, 1983;CrossRefGoogle Scholar
  63. (b).
    Middleton E, The flavonoids. Trends in Pharmacological Res. 335–338, 1984.Google Scholar
  64. 50.
    Hahlbrock K, Flavonoids. In: The Biochemistry of Plants (ed Conn EE) Vol 7, Ch. 14, Academy Press, New York, NY, pp. 425–456, 1981.Google Scholar
  65. 51.
    a) Wattenberg LW and Leong JL, Inhibition of the carcinogenic action of 7,12-dimethylbenz[a]anthracene by beta-naphthoflavone. Proc. Soc. Exptl. Biol. Med. 128: 940–943, 1968;Google Scholar
  66. (b).
    Mitscher LA, Rao GSR, Khanna I, Vegsoglu T and Drake S, Antimicrobial agents from higher plants: prenylated flavonoids and other phenols from Glycyrrhiza lepidota. Phytochemistry 22: 573–576, 1983;CrossRefGoogle Scholar
  67. (c).
    Huang MT, Wood AW, Newmark HL, Sayer JM, Yagi H, Jerina DM and Conney AM, Inhibition of the mutagenicity of bay-region diol-epoxides of polycyclic aromatic hydrocarbons by phenolic plant flavonoids. Carcinogenesis 4: 1631–1637, 1983.PubMedCrossRefGoogle Scholar
  68. 52.
    a) Simpson TH and Uri N, Hydroxyflavones as inhibitors of the aerobic oxidation of unsaturated fatty acids. Chem. Ind. 956–957, 1956;Google Scholar
  69. (b).
    Mehta AC and Seshadri TR, Flavonoids as antioxidants. J. Sci. Indian Res. 18B: 24–28, 1959;Google Scholar
  70. (c).
    Borchardt RT and Huber JA, Catechol O-methyltransferase 5. Structure-activity relationships for inhibition by flavonoids. J. Med. Chem. 18: 120–122, 1975;PubMedCrossRefGoogle Scholar
  71. (d).
    Varma SD and Kinoshita JH, Inhibition of lens aldose reductase by flavonoids —their possible role in the prevention of diabetic cataracts. Biochem. Pharmacol. 25: 2505–2513, 1976;PubMedCrossRefGoogle Scholar
  72. (e).
    Kellis JT and Vickery LE, Inhibition of human estrogen synthetase (aromatase) by flavones. Science 225: 1032–1034, 1984.PubMedCrossRefGoogle Scholar
  73. 53.
    is WD, The isoflavonoids. In: The Chemistry of Flavonoids Compounds (ed Geissman TA ) pp. 353–405, MacMillan, New York, NY, 1962.Google Scholar
  74. 54.
    a) Diamond L and Gelboin HV, Alpha-naphthoflavone: An inhibitor of hydrocarbon cytotoxicity and microsomal hydroxylase. Science 166: 1023–1025, 1969;PubMedCrossRefGoogle Scholar
  75. (b).
    Diamond L, Miller J and Gelboin HV, The effects of two isomeric benzoflavones on aryl hydrocarbon hydroxylase and the toxicity and carcinogenicity of polycyclic hydrocarbones. Cancer Res. 32: 731–736, 1972;PubMedGoogle Scholar
  76. (c).
    Schwartz AG, Protective effect of benzoflavone and estrogen against 7,12-dimethylbenz(a)anthracene-induced cytotoxicity in cultured liver cells. Cancer Res. 34: 10–15, 1974.PubMedGoogle Scholar
  77. 55.
    a) Wattenberg LW, Page MA and Leong JL, Induction of increased benzopyrene hydroxylase activity by flavones and related compounds. Cancer Res. 28: 934–937, 1968;PubMedGoogle Scholar
  78. (b).
    Wattenberg LW and Leong JL, Inhibition of the carcinogenic action of benzo(a)pyrene by flavones. Cancer Res. 30: 1922–1925, 1970.PubMedGoogle Scholar
  79. 56.
    a) Double JA, Bibby MC and Loadman PM, Pharmacokinetics and antitumor activity of LM595 in mice bearing transplantable adenocarcinomas of the colon. Brit. J. Cancer 54: 595–600, 1986; (b) Plowman J, Narayanan VL, Dykes D, Szarvasi E, Briet P, Yoder OC and Paull KD, Flavoneacetic acid: A novel agent with preclinical antitumor activity against colon adenocarcinoma 38 in mice. Cancer Treat. Rep. 70: 631–635, 1986.Google Scholar
  80. 57.
    a) Brewer AD, Minatelli JA, Plowman J, Paull KD and Narayanan VL, 5-(N-Phenylcarboxamido)-2-thiobarbituric acid (NSC 336628), a novel potential antitumor agent. Biochem. Pharmacol. 34: 2047–2050, 1985;PubMedCrossRefGoogle Scholar
  81. (b).
    Cooney DA, Covey JM, Kang GJ, Dalai M, McMahon JB and Johns DJ, Initial mechanistic studies with merbarone (NSC 336628). Biochem. Pharmacol. 34: 3395–3398, 1985.PubMedCrossRefGoogle Scholar
  82. 58.
    Brewer AD, Ferguson G and Parvez M, Triethylammonium salt of 1,2,3,4-tetrahydro-6-hydroxy4-oxo-N-phenyl-2-thio-5-pyrimidinecarboxamide, ethanol solvate. Acta Crystallogr. C43: 144147, 1987.Google Scholar
  83. 59.
    Huggins C and Yang NC, Induction and extinction of mammary cancer. Science 137: 257–262, 1962.PubMedCrossRefGoogle Scholar
  84. 60.
    Haddow A, New facts and concepts: A general survey. Canadian Cancer Conference 2: 361–374, 1957.Google Scholar
  85. 61.
    a) Gellert M, DNA topoisomerases. Ann. Rev. Biochem. 50: 879–910, 1981; (b) Liu LF, DNA topoisomerases enzymes that catalyze the breaking and rejoining of DNA. CRC Critical Rev. Biochem. 5: 1–24, 1983; (c) Chen GL and Liu LF, DNA topoisomerases as therapeutic targets in cancer chemotherapy. Ann. Rep. Med. Chem. 21: 257–262, 1986.CrossRefGoogle Scholar
  86. Tewey KM, Chen GL, Nelson EM and Liu LFGoogle Scholar
  87. 62.
    a) Tewey KM, Chen GL, Nelson EM and Liu LF, Intercalative antitumor drugs with the breakage-reunion reaction of mammalian DNA topoisomerase II. J. Biol. Chem. 259: 9182–9187, 1984;PubMedGoogle Scholar
  88. (b).
    Ross WE, DNA topoisomerases as targets for cancer chemotherapy. Biochem. Pharmacol. 34: 4191–4195, 1985;PubMedCrossRefGoogle Scholar
  89. (c).
    Alexander RB, Nelson WG and Coffey DS, Synergistic enhancement by tumor necrosis factors of in vitro cytotoxicity from chemotherapeutic drugs targeted at DNA topoisomerase II. Cancer Res. 47: 2403–2406, 1987.PubMedGoogle Scholar
  90. 63.
    a) Pommier Y, Schwartz RE, Swelling LA and Kohn KW, Effects of DNA intercalating agents on topoisomerase II induced DNA strand cleavage in isolated mammalian cell nuclei. Biochemistry 24: 6406–6410, 1985;PubMedCrossRefGoogle Scholar
  91. (b).
    Mattem MR, Mong SM, Bartus HF, Mirabelli CK, Crooke ST and Johnson RK, Relationship between the intercellular effects of camptothecin and the inhibition of DNA topoisomerase I in cultural L 1210 cells. Cancer Res. 47: 1793–1798, 1987.Google Scholar
  92. 64.
    Glusker JP, Structure aspects of steroid hormones and carcinogenic polycyclic aromatic hydrocarbons. In: Biochemical Actions of Hormones (ed Litwack G), Vol. VI, Ch. 3, pp. 121–204, Academy Press, New York, NY 1979.Google Scholar
  93. 65.
    Yang NC, Castro AJ, Lewis M and Wong TW, Polynuclear aromatic hydrocarbons, steroids and carcinogenesis. Science 134: 386–387, 1961.PubMedCrossRefGoogle Scholar
  94. 66.
    a) Glascock RF and Hoekstra WG, Selective accumulation of tritium-labelled hexosterol by the reproductive organs of immature female goats and sheep. Biochem. J. 72: 673–682, 1959; (b) Toft D and Gorski J, A receptor molecule for estrogens: Isolation from the rat uterus and preliminary characterization. Proc. Natl. Acad. Sci. USA 55: 1574–1581, 1966.CrossRefGoogle Scholar
  95. 67.
    Ebright RH, Wong JR and Chen LB, Binding of 2-hydroxybenzo(a)pyrene to estrogen receptors in rat cytosol. Cancer Res. 46: 2349–2351, 1986.PubMedGoogle Scholar
  96. 68.
    a) Nissen ED and Kent DR, Liver tumors and oral contraceptives. Obstet. Gynecol. 46: 460–467, 1975;PubMedGoogle Scholar
  97. (b).
    Siiteri PK, Steroid hormones and endometrial cancer. Cancer Res. 38: 4360–4366, 1978.PubMedGoogle Scholar
  98. 69.
    Pott P, Cancer scroti. Chirugical Observations Relative to the Cancer of the Scrotum. 63–68, 1775.Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1992

Authors and Affiliations

  • C. C. Cheng
    • 1
  1. 1.Drug Development Laboratory and Department of PharmacologyToxicology & Therapeutics University of Kansas Medical CenterKansas CityUSA

Personalised recommendations