Τόμος 2 (1984) – Τεύχος 1 – Άρθρο 5 – Επιθεώρηση Κλινικής Φαρμακολογίας και Φαρμακοκινητικής-Ελληνική Έκδοση – Volume 2 (1984) – Issue 1 – Article 5 – Epitheorese Klinikes Farmakologias και Farmakokinetikes-Greek Edition

Τίτλος – Title Κυτταροστατικά: Αλκυλιωτικές Ουσίες

Cytostatics: Alkylating Agents

Συγγραφέας – Author Αθανάσιος Δ. Παπαγεωργίου

Συμεωνίδειο Ερευνητικό Κέντρο, Θεαγένειο Ιατρικό Ινστιτούτο Θεσσαλονίκης

Athanassios D. Papageorgiou

Theagenion Medical Institut, Thessaloniki

Παραπομπή – Citation Παπαγεωργίου, Α.: Κυτταροστατικά: Αλκυλιωτικές Ουσίες, Επιθεώρηση Κλιν. Φαρμακολ. Φαρμακοκινητ. 2(1): 53-66 (1984)

Papageorgiou, A.: Cytostatics: Alkylating Agents, Epitheorese Klin. Farmakol. Farmakokinet. 2(1): 53-66 (1984)

Ημερομηνία Δημοσιευσης – Publication Date Απρίλιος 1984 – April 1984
Γλώσσα Πλήρους Κειμένου –
Full Text Language
Ελληνικά – Greek
Παραγγελία – Αγορά –
Order – Buy
Ηλεκτρονική Μορφή: pdf (15 €) –
Digital Type: pdf (15 €)
pharmakonpress[at]pharmakonpress[.]gr
Λέξεις κλειδιά – Keywords Αλκυλιωτικές ουσίες

Alkylating Agents

Λοιποί Όροι – Other Terms Άρθρο
Article
Περίληψη – Summary The literature on alkylating agents is very extensive, partly because of their wide range of clinical applications and partly because of their basic scientific interest. Several review articles are available that are included in the reference section. The purpose of this review is: to outline our knowledge of the alkylating agents, and to present certain areas of active research in greater detail. It is tempting to try to pull the maximum number of these observations together in some theoretical framework, and we have done this here by focusing on: 1. The classification of alkylating agents; 2. The mechanism of action. Alkylating agents have been shown to react with a wide range of cellular components (nucleophylic sites). Thus, cellular proteins and nucleic acids are alkylated as well as most of the low-molecular wheight compounds. DNA is the primary target of the alkylation and some details of these interactions are described here; 3. The distribution and cellular uptake of alkylating agents; and 4. Their clinical applications.
Αναφορές – References 1.         Gilman, A., Philips, F.S.: The biological actions and therapeutic applications of the b-chloroethylamines and sulfides. Science 103: 409 (1946)

2.         Ross, W.C.J.: The chemistry of cytotoxic alkylating agents. Advene. Cancer Res. 1: 397 (1953)

3.         Gilman, A.: The initial clinical trials of nitrogen mustard. Am. J. Surg. 105: 574 (1963)

4.         Jacobson, L.O., Spurr. C.L, Barron, E.S.G., Smith, T.R., Lushbaugh, C., Dick, G.F.: Nitrogen mustard therapy: Studies on the effect of methylbis (betachloroethyl) amine hydrochloride on neoplastic diseases and allied disorders of the hemopoietic system. JAMA 132: 263 (1946)

5.         Rhoads, C.P.: Nitrogen mustards in treatment of neoplastic disease: official statement. JAMA 131: 656 (1946)

6.         Wheller, G.P.: Alkylating Agents. In: Cancer Medicine (Holland, J.F., Freí, E., Ill eds). Lea and Febiger. Philadelphia, p. 791 (1973)

7.         Connors, T.A.: Mechanism of action of 2-chtoroethylamine derivatives, sulfur mustards, epoxides and aziridrnes. In: Antineoplastic and Immunosuppressive Agents, pt. II. (Sartorelli, A.C.. Johns, D.G., eds). Handb. Exp. Pharmacol., Vol. 38, Springer-Verlag, Berlin, p. 18(1975)

8.         Ross, W.C.J.: Rational desing of alkylating agents. In, Antineoplastic and Immunosupressive Agents. Pt. II, (Sartorelli, A.C., Johns, D.G., eds). Handb. Exp. Pharm., Vol. 38, Springer-Verlag, Berlin, p. 33 (1975)

9.         Ludlum, D.B.: Alkylating agents and the nitrosoureas. In: Cancer: A Comprehensive Treatise, (Becker, F.F. ed.) Vol. 5, p. 285 (1977)

10.       Ludlum, D.B.: The Alkylating agents and nitrosoureas. In: Cancer Chemotherapy 111. (Brodsky, L, Kahn, S.B., Conroy, J.F., eds). Gruñe and Stratton. Inc., New York, p. 17 (1978)

11.        Calabresi, P., Parks, R.E. Jr.: Chemotherapy of neoplastic disease. In: The Pharmacological Basis of Therapeutics (Goodman and Gilman’s, eds). Sixth ed., p, 1249 (1980)

12.       Wheller, G.P.: Alkylating Agents. In: Cancer Medicine (J. F. Holland, E. Frei. Ill, eds). p. 824 (1982)

13.       Wood, H.B.: Selection of agents for the tumor screen of potential new antineoplastic drugs. Methods of Development of New Anticancer Drugs. USE-USSR Monograph, p. 15 (1977)

14.       Carter, S.K., Slavik, M.: Current investigational drugs of interest in the chemotherapy program of the National Cancer Institute. Methods of Developement of New Anti-cancer Drugs. USA-USSR monograph., p. 101 (1977)

15.       Wheller, G.P.: Some biochemical effects of alkylating agents. Fed. Proc. 26: 885 (1967)

16.       Wheller, G.P., Chumley, S.: Alkylating activity of 1,3-bis (2-chloroethyl)-1-nitrosoureas and related compounds. J. Med. Chem. 10: 259 (1967)

1 7. Loveless, A.: Genetic and Allied Effects of Alkylating Agents. University Park, The Pennsylvania State University Press (1966)

18.       Lawley, P.D.: Effects of some chemical mutagens and carcinogens on nucleic acids. Progr. Nud. Acid. Res. 5: 89 (1966)

19.       Lawley, P.D.: Gome chemical aspects of dose response relationships in alkylation mutagenesis. Mutat. Res. 23: 283 (1974)

20.      Drake, J.W.; The Molecular Basis of Mutation. Holden -Day. San Francisco (1970)

21.       Lawley, P.D., Thatcher, C.J.: Méthylation of deoxyribonucleic acid in cultured mammalian cells by N-methyl

N’-nitro-N-mtroso-guanidine. The influence of cellular thiol concentrations on the extend of méthylation and the 6-oxygen atom of guanine as a site of méthylation. Biochem. J. 7 76. 693 (1970)

22.       Singer, B.: The chemical effects of nucleic acid alkylation and their relation to mutagenesis and carcinogenesis. Progr. Nuci. Acni. Res. Mol. Biol. 75: 219 (1975)

23.       Brookes, R, Lawley, P.D.: Alkylating Agents. Brit. Med. Bull. 20. 91 (1964)

24.       Lawley, P.D.: Carcinogenesis by alkylating agents. In: Clinical Carcinogens. Edited by C.E, Searle. Amer. Chem. Soc. Monograph 7 73: 83 (1976)

25.       Fishbein, L,, Flamm, W.G., Folk, H.E.: Chemical Mutagens: Environmental Effects on Biological Systems, Academic Press, New York (1970)

26.       WF10. 1RAC, Sci. Publ. Evaluation of Carcinogenic Risk of Chemicals to Man. 9, Lyon, France (1975)

27.       Di Paolo, J.A.: Teratogenic agents: mammalian test systems and chemicals. N.Y. Acad. Sci. 763: 801 (1966)

28.      Connors, T.A.: Protection against the toxicity of alkylating agents by thiols: the mechanism of protection and its relevance to cancer chemotherapy. A review. Eur. J. Cancer 2: 293 (1966)

29.       Connors, T.A.: The need of additional alkylating agents. Cancer Res. 29: 2443 (1969)

30.      Karnofsky, D.A.: Comparative clinical and biological, effects of alkylating agents Ann. N.Y. Acad. Set. 68. 657 (1958)

31.       Wheller, G.P.: Studies related to the mechanisms of action of cytotoxic alkylating agents. A review. Cancer Res. 22: 651 (1962)

32.       Roberts, J.J., Crathorn, A.R., Brent, T.P.: Repair of alkylated DNA in mammalian cells. Nature 218: 970 (1968)

33.       Verly, W.G., Brakier, L.: Mechanismes moléculaires de l ‘ action toxique des agents alkylants. Rev. Europ. Eludes Chn. et Biol. 75: 483 (1970)

34.       Ludlum, D.8.: Mechanism of action of chemotherapeutic drugs. Mechanism of action of alkylating agents. In: Cancer Chemother. (I. Brodsky, S.B. Kahn, J.H. Mayer, eds). II. p. 1, Grune and Stratton, New York (1972)

35.       Wheller, G.P., Alexander, J.A.: Effects of nitrogen mustard and cyclophosphamide upon the synthesis of DNA in vivo and in cell-free preparations. Cancer Res. 29: 98 (1969)

36.       Verly, W.G., Brakier, L: The lethal action of monofunctional and bifunctional alkylating agents on T, coliphage. Biochim. Biophys. Acta 7 74: 674 (1969)

37.       Ewig, R.A.G., Kohn, K.W.: DNA damage and repair in mouse Leukemia L^o cells treated with Nitrogen Mustard, 1,3-bis (2-chloroethyl)-1 -nitrosourea and other nitrosoureas. Cane. Res. 37: 2114 (1977)

38.      Ross, W.C.J.: Biological Alkylating Agents. London, Butterworths, p. 177 (1962)

39.       Price, C.C.: Chemistry of alkylation. In. Antmeoplastic and Immunosuppressive Agents, II. Handb. Exp. Pharm, 38/2 (A.C. Sartorelli, D.C, Johns, eds), p. 1, Springer – Verlag, Berlin (1975)

40.      Shapiro, R.: Chemistry of guanine and its biologically significant derivatives. Progr. Nuci. Acid. Res. Mol. Biol. 8: 73 (1968)

41.       Naclkarni, M.V., Trams, E.G., Smith, P.K.: Preliminary studies on the distribution and fate of TEM, TEPA and myleran in the human. Cancer Res. 19: 713 (1959)

42.       Brookes, P., Lawley, P.D.: The reaction of mono- and difunctional alkylating agents with nucleic acids. Biochem. J. 80: 495 (1971)

43.       Lawley, P.D., Brooks, P.: Further studies on the alkylation of nucleic acids and their constituent nucleotides. Biochem. J. 89: 127 (1963)

44.       Singer, B.: O–Alkylcytidine: A new major product of neutral aqueous reaction of cytidine with carcinogens. FEBS Lett. 63: 85 (1976)

45.       Kusmierek, J.T., Singer, B.: Sites of alkylation of poly U by agents of varying carcinogenecity and stability of products. Biochim. Biophys. Acta 442: 420 (1976)

46.       Goldacre, R.J., Loveless, A., Ross, W.C.J.: Mode of  production of chromosome abnormalities by the nitrogen mustards. The principle role of linking. Nature 163: 667 (1949)

47.       Lyer, V.N., Szybalski, W.A.. A molecular mechanism of Mitomycin action: Linking of complementary DNA strands. Proc. Natl. Acad. Sci.. U.S. 50: 355 (1963)

48.      Kohn, K.W., Spears, C.L. and Doty, P.: Inter-stand cross-linking of DNA by nitrogen mustard. J. Mol. Biol. 19: 266 (1966)

49.       Walker, L.G.: Intrastand bifunctional alkylation of DNA in mammalian cells treated with mustard gas. Canad. J. Biochem. 49: 332 (1971)

50.       Papageorgiou, A., Ivanov, I., Markov, G., Koliais, S.I., Boutis, L., Catsoulacos, P., Interaction of homo-aza-steroidal ester of (p(bis-(2-chloroethyl) aminophenyl acetic acid (ASE) with DNA of Ehrlich ascites tumor cells. FEBS Letters 153: 194 (1983)

51.       Jolley, G,M,, Ormerod, M.G.: An improved method for measuring cross-links in the DNA of mammalian cells: The effect of nitrogen mustard. Biochim. Biophys. Acta 308: 242 (1973)

52.       Papageorgiou, A., Ivanov, I., Markov, G., Boutis, L., Catsoulacos, P,: Does ASE (an alkylating ester) from interstrand crosslinks in the DNA of Ehrlich ascites tumor cells (EAT). In: Anticancer Research, Vol. 4, Suppl. 1 (1984)

53.       Kohn, K.W.: Interstrand cross-linking of DNA by 1,3-bis (2-chloroethyl)-1-nitrosoureas and other 1-(2-haloethyl)-1-nitrosoureas Carre. Res. 37: 1450 (1977)

54.       Papageorgiou, A., Koliais, S.I., Antonoglu, O., Catsoulacos, P., Boutis, L.: Studies on the effect of homo-azasteroidal ester of p-bis-(2-chloroethyl) aminophenyl acetic acid. In: Methods and Findings in Experimental and Clinical pharmacology. Vol. 5, No 10 (1983)

55.       Thomas. C.B.. Osilka, R., Kohn, K.W. DNA crossltnking by in vivo treatment with 1-(2 ch:uioethyl) 3 (4 methyl cyclohexyl)-1-nitrosourea ut sensitive and resistance human carcinoma xenogralts m nude mice Cane. Res. 38: 2448 (1978)

56.       Ewig, R.A., Kohn, K.W.: DNA-protein crosslinking, and DNA interstrand crosslinking by haloethylnitrosoureas in L1210 cells. Cancer Res. 38; 3197 (1978)

57.       Thomas, C.B., Kohn, K.W., Bonner, W.M.: Characterization of DNA-protein cross-links formed by treatment of Li2,0 cells and nuclei with bis (2-chloroethyl) methylamine (nitrogen mustard). Biochemistry: 3954 (1978)

58.       Ludlum, D.B.: Reaction of nitrogen mustard with synthetic polynucleotides. Biochim. Biophys. Acta 142: 282 (1967)

59.       Ludlum, D.B.: Etl ylation of pylyadenylic acid. Biochim. Biophys. Acta 174: 773 (1969)

60.      Fornace, A.J.: Detection of DNA single-strand breaks produced during the repair of damage by DNA-protem cross-linking agents. Cane. Res. 42: 145 (1982)

61.       Fram, R.J., Kufe, D.W.: DNA strand breaks caused by inhibitors of DNA synthesis: 1-B-D-arabinofuranosylcytosine and aphidicolin. Cane. Res. 42: 4050 (1982)

62.       Rhaese, H.J., Freeze, E.: Chemical analysis of DNA alterations. IV. Reactions of oligodeoxynucleotides with monofunctional alkylating agents leading to backbone breakage. Biochim. Biophys. Acta 190: 418 (1969)

63.       Bannon, P., Verly, W.: Alkylation of phosphates and stability of phosphate trlesters in DNA. Eur. J. Biochem. 31: 103 (1972)

64.       Strauss, B.S., Coyle, M,, Robbins, M.: Consequences of alkylation for the behavior of DNA, Ann. N.Y. Acad. Sci. 163: 765 (1969)

65.       Friedberg, E.C., Goldthwait, D.A.: Endonuclease 11 of E. Coli, I. Isolation and purification. Proc. Natl. Acad. Sci. USA 62: 934 (1969)

66.       Verly, W.G., Paquette, Y.: An endonuclease for depurinated DNA in E. Coli. B. Can. J. biochem. SO: 217 (1972)

67.       Wheller, G.P.: Studies related to mechanisms of resistance to biological alkylating agents. Cancer Res. 23: 1334 (1963)

68- Harrap, K.R. and Gascoigne, E.W.: The interaction of bifunctional alkylating agents with DNA of tumor cells. Eur. J. Cancer 12: 53 (1976)

69.       Golder, R.H., Martin-Guzman, G., Jones, J., Goldstein, N.O., Rotenberg, S. and Rutman, R.J.: Experimental Chemotherapy studies. III. Properties of DNA from Ascites cells treated in vivo with nitrogen mustard. Cane. Res. 24: 964 (1964)

70.       Altmann, H., Schattauer, F., Eds: Repair Mechanisms. Schattauer, Stuttgart-New York (1972)

71.       Hanawalt, P.C., Setlow, R.B., Eds: Molecular Mechachanisms for Repair of DNA. Plenum Press, New York (1975)

72.       Ludlum, D.B.: The properties of 7-methylguanine-containing templates fro ribonucleic acid polymerase. J. Biol. Cham. 245: 477 (1970)

73.       Ludlum, D.B.: Alkylated polycytidylic acid templates for RNA polymerase. Biochim. Acta 213: 142 (1970)

74.       Ludlum, D.B.: Methylated polydeoxyribocytidylic acid templates for RNA polymerase. Biochim. Biophys. Acta 274: 412 (1971)

75.       Schabel, F.M., Johnston, T.P., McCaleb, G.S., Montgomery, J.A., Laster, W.R., Skipper, H.E.: Experimental evaluation of potential anticancer agents. VIII. Effects of certain nitrosoureas on intracerebral L,210 Leukemia. Cancer Res. 23: 725 (1963)

76.       Walker, M.D.: Nitrosoureas in central nervous system tumors. Cancer Chemother. Rep., Suppl. 4: 21 (1973)

77.       Hansch, C„ Smith, N., Engle, R., Wood, H.: Quantitative structure-activity relationships of antineoplastic drugs: Nitrosoureas and Triazenoimidazoles. Cancer Chemother. Rep. Part 1. 56: 442 (1972)

78.       Wheller, G.P., Bowden, B.J., Grimsley, J.A., Lloyd, K.H.: Interrelationships of some chemical, physicochemical and biological activities of several 1 -(2-haloethyl)-1 -nitrosoureas. Cancer Res. 34: 194 (1974)

79.       Goldenberg, G.J., Vanstone, C.L., Israels, L.G., lise, D., Bihler, I.: Evidence for a transport carrier of nitrogen mustard in nitrogen mustard-sensitive and resistant Uwe Y lymphoblasts. Cancer Res. 30; 2285 (1970)

80.      Goldenberg, G.J., Lyons, R.M., Lepp, J.A., Vanstone, C.L: Sensitivity to nitrogen mustard as a function of transport activity and proliferative rate in L&1JB Y lymphoblasts, Cancer Res. 31: 1616 (1971)

81.       Gondenberg, G.J., Land, H.B., Cormack, D.V.: Mechanism of cyclophosphamide transport by L5178 Y Lymphoblasts in vitro. Cancer Res. 34: 3274 (1974)

82.      Goldenberg, G.J.: The role of drug transport in resistance to nitrogen mustard and other alkylating agents in L5178 Y lymphoblasts. Cancer Res. 35: 1687 (1975)

83.      Lyons, R.M., Goldenberg. G.J.: Active transport of nitrogen mustard and choline by normal and leukemic human lymphoid cells. Cancer Res. 32: 1679 (1972)

84.      Mathé, G.: La Chimiothérapie de Cancers. L’ Expansion Scientifique Française. Paris (1968)

85.       Livingston, R.B., Carter, S.K.: Single Agents in Cancer Chemotherapy. Plenum, London and New York (1970)

85. Aaron, H.: The choice of therapy in the treatment of cancer. Med. Let. 12: 13 (1970)

87.       Bonadona, G., Brusamolmo, E., Valagussa, P., Rossi, A., Brugnatelli, L., Brambilla, G., Delena, M., Tancini, G., Bajetta, E., Musumesi, U.: Combination chemotherapy as an adjuvant treatment in operable breast cancer, N. Engl. J. Med. 294: 405 (1976)

88.      Larionov, L.F.: Cancer Chemotherapy. Pergamon Press, p, 312 (1965)

89.      Cole, W.H.: Chemotherapy of Cancer. Lea and Febiger Philadelphia (1970)

90.      Elkebroud, F,, Thomas, P., Zwaveling, A.: Cancer Chemotherapy. Leiden University Press, Leiden (1971)

91.       Sanorelli, A.C.: Approaches to the combination chemotherapy of transplantable neoplasms. Progr. Exp. Tumor. Res. 6: 288 (1965)

92.       Price, C.C.: Fundamental mechanisms of alkylation, Ann. N.Y. Acad. Sci. 68: 663 (1958).

Online ISSN 1011-6575

Άρθρα Δημοσιευμένα σε αυτό το Περιοδικό Καταχωρούνται στα:

Articles published in this Journal are Indexed or Abstracted in:
• Chemical Abstracts
• Elsevier’s Bibliographic Databases: Scopus, EMBASE, EMBiology, Elsevier BIOBASE
SCImago Journal and Country Rank Factor

Τι είναι η Επιθεώρηση Κλινικής Φαρμακολογίας και Φαρμακοκινητικής-Ελληνική Έκδοση-Οδηγίες προς τους Συγγραφείς 
What is Epitheorese Klinikes Farmakologias και Farmakokinetikes-Greek Edition-Instrunctions to Authors

Άρθρα Δημοσιευμένα στην Επιθεώρηση Κλινικής Φαρμακολογίας και Φαρμακοκινητικής-Ελληνική Έκδοση
Articles Published in Epitheorese Klinikes Farmakologias και Farmakokinetikes-Greek Edition

Συντακτικη Επιτροπή-Editorial Board

ΕΤΗΣΙΑ ΣΥΝΔΡΟΜΗ 1984 – ANNUAL SUBSCRIPTION 1984
Γλώσσα Πλήρους Κειμένου – 
Full Text Language
Ελληνικά – Greek
Παραγγελία – Αγορά –
Order – Buy
Ηλεκτρονική Μορφή: pdf (70 €) –
Digital Type: pdf (70 €)pharmakonpress[at]pharmakonpress[.]gr
Έντυπη Μορφή (70 € + έξοδα αποστολής)
Printed Type (70 € + shipping)pharmakonpress[at]pharmakonpress[.]gr

 

 

Προσθέστε στους σελιδοδείκτες το μόνιμο σύνδεσμο.

Τα σχόλια είναι απενεργοποιημένα.