Inhibition of human DNA polymerase β activity by the anticancer prodrug Cloretazine

Biochemical and Biophysical Research Communications

Volumn 378, Issue 3, 2009, Pages 419-423

  Frederick, Abbie M ^a   Davis, Marguerite L ^a   Rice, Kevin P ^a  

^a Colby College   (United States)

Author keywords

Carbamoylation; Cloretazine; DNA alkylation; DNA base excision repair; DNA crosslinking agents; DNA polymerase beta; Methyl isocyanate

Indexed keywords

CLORETAZINE; DNA DIRECTED DNA POLYMERASE BETA; GUANINE; NUCLEOTIDYLTRANSFERASE;

ARTICLE; CONTROLLED STUDY; CYTOTOXICITY TEST; DNA ALKYLATION; DNA CROSS LINKING; ENZYME ACTIVITY; ENZYME INHIBITION; EXCISION REPAIR; IN VIVO STUDY; NONHUMAN; PRIORITY JOURNAL;

ANTINEOPLASTIC AGENTS; DNA POLYMERASE BETA; DNA POLYMERASE I; DNA REPAIR; HUMANS; HYDRAZINES; INHIBITORY CONCENTRATION 50; PRODRUGS; SULFONAMIDES;

EID: 57749209136     PISSN: 0006291X     EISSN: 10902104     Source Type: Journal    
DOI: 10.1016/j.bbrc.2008.11.042     Document Type: Article

References (34)

1. Eisenbrand G., Muller N., Denkel E., and Sterzel W. DNA adducts and DNA damage by antineoplastic and carcinogenic N-nitroso compounds. J. Cancer Res. Clin. Oncol. 112 (1986) 196-204
2. Penketh P.G., Shyam K., and Sartorelli A.C. Comparison of DNA lesions produced by tumor-inhibitory 1,2-bis(sulfonyl)hydrazines and chloroethylnitrosoureas. Biochem. Pharmacol. 59 (2000) 283-291
3. Bodell W.J., Tokuda K., and Ludlum D.B. Differences in DNA alkylation products formed in sensitive and resistant human glioma cells treated with N-(2-chloroethyl)-N-nitrosourea. Cancer Res. 48 (1988) 4489-4492
4. Penketh P.G., Baumann R.P., Ishiguro K., Shyam K., Seow H.A., and Sartorelli A.C. Lethality to leukemia cell lines of DNA interstrand cross-links generated by Cloretazine derived alkylating species. Leuk. Res. 32 (2008) 1546-1553
5. Gombar C.T., Tong W.P., and Ludlum D.B. Mechanism of action of the nitrosoureas-IV. Reactions of bis-chloroethyl nitrosourea and chloroethyl cyclohexyl nitrosourea with deoxyribonucleic acid. Biochem. Pharmacol. 29 (1980) 2639-2643
6. Rice K.P., Penketh P.G., Shyam K., and Sartorelli A.C. Differential inhibition of cellular glutathione reductase activity by isocyanates generated from the antitumor prodrugs Cloretazine and BCNU. Biochem. Pharmacol. 69 (2005) 1463-1472
7. Hilton J., Maldarelli F., and Sargent S. Evaluation of the role of isocyanates in the action of therapeutic nitrosoureas. Biochem. Pharmacol. 27 (1978) 1359-1363
8. Gibson N.W., and Hickman J.A. The role of isocyanates in the toxicity of antitumour haloalkylnitrosoureas. Biochem. Pharmacol. 31 (1982) 2795-2800
9. Kann Jr. H.E., Kohn K.W., and Lyles J.M. Inhibition of DNA repair by the 1,3-bis(2-chloroethyl)-1-nitrosourea breakdown product, 2-chloroethyl isocyanate. Cancer Res. 34 (1974) 398-402
10. Johnston T.P., and Montgomery J.A. Relationship of structure to anticancer activity and toxicity of the nitrosoureas in animal systems. Cancer Treat. Rep. 70 (1986) 13-30
11. Shyam K., Penketh P.G., Loomis R.H., Rose W.C., and Sartorelli A.C. Antitumor 2-(aminocarbonyl)-1,2-bis(methylsulfonyl)-1-(2-chloroethyl)hydrazines. J. Med. Chem. 39 (1996) 796-801
12. Giles F.J. Bendamustine and cloretazine: alkylators with sharply contrasting activity in AML. Leuk. Lymphoma 48 (2007) 1064-1066
13. Sorbera L.A., and Serradell N. VNP-40101M. DNA alkylating agent, oncolytic. Drug Future 31 (2006) 1062-1068
14. Mao J., Xu Y., Wu D., and Almassain B. Pharmacokinetics, mass balance, and tissue distribution of a novel DNA alkylating agent, VNP40101M, in rat. AAPS PharmSci. 4 (2002) E24
15. Murren J., Modiano M., Kummar S., Clairmont C., Egorin M., Chu E., and Sznol M. A phase I and pharmacokinetic study of VNP40101M, a new alkylating agent, in patients with advanced or metastatic cancer. Invest. New Drugs 23 (2005) 123-135
16. Pegg A.E. Repair of O(6)-alkylguanine by alkyltransferases. Mutat. Res. 462 (2000) 83-100
17. Ishiguro K., Shyam K., Penketh P.G., and Sartorelli A.C. Role of O6-alkylguanine-DNA alkyltransferase in the cytotoxic activity of cloretazine. Mol. Cancer Ther. 4 (2005) 1755-1763
18. Penketh P.G., Shyam K., Baumann R.P., Remack J.S., Brent T.P., and Sartorelli A.C. 1,2-Bis(methylsulfonyl)-1-(2-chloroethyl)-2-[(methylamino)carbonyl]hydrazine (VNP40101M): I. Direct inhibition of O6-alkylguanine-DNA alkyltransferase (AGT) by electrophilic species generated by decomposition. Cancer Chemother. Pharmacol. 53 (2004) 279-287
19. Giles F., Verstovsek S., Thomas D., Gerson S., Cortes J., Faderl S., Ferrajoli A., Ravandi F., Kornblau S., Garcia-Manero G., Jabbour E., O'Brien S., Karsten V., Cahill A., Yee K., Albitar M., Sznol M., and Kantarjian H. Phase I study of cloretazine (VNP40101M), a novel sulfonylhydrazine alkylating agent, combined with cytarabine in patients with refractory leukemia. Clin. Cancer Res. 11 (2005) 7817-7824
20. Baumann R.P., Seow H.A., Shyam K., Penketh P.G., and Sartorelli A.C. The antineoplastic efficacy of the prodrug Cloretazine (TM) is produced by the synergistic interaction of carbamoylating and alkylating products of its activation. Oncol. Res. 15 (2005) 313-325
21. Baumann R.P., Shyam K., Penketh P.G., Remack J.S., Brent T.P., and Sartorelli A.C. 1,2-Bis(methylsulfonyl)-1-(2-chloroethyl)-2-[(methylamino)carbonyl]hydrazine (VNP40101M): II. Role of O6-alkylguanine-DNA alkyltransferase in cytotoxicity. Cancer Chemother. Pharmacol. 53 (2004) 288-295
22. Fortini P., Pascucci B., Parlanti E., D'Errico M., Simonelli V., and Dogliotti E. The base excision repair: mechanisms and its relevance for cancer susceptibility. Biochimie 85 (2003) 1053-1071
23. Almeida K.H., and Sobol R.W. A unified view of base excision repair: lesion-dependent protein complexes regulated by post-translational modification. DNA Repair 6 (2007) 695-711
24. Prasad R., Beard W.A., Strauss P.R., and Wilson S.H. Human DNA polymerase beta deoxyribose phosphate lyase. Substrate specificity and catalytic mechanism. J. Biol. Chem. 273 (1998) 15263-15270
25. Ochs K., Sobol R.W., Wilson S.H., and Kaina B. Cells deficient in DNA polymerase beta are hypersensitive to alkylating agent-induced apoptosis and chromosomal breakage. Cancer Res. 59 (1999) 1544-1551
26. Horton J.K., Joyce-Gray D.F., Pachkowski B.F., Swenberg J.A., and Wilson S.H. Hypersensitivity of DNA polymerase beta null mouse fibroblasts reflects accumulation of cytotoxic repair intermediates from site-specific alkyl DNA lesions. DNA Repair 2 (2003) 27-48
27. Baril B.B., Baril E.F., Laszlo J., and Wheeler G.P. Inhibition of rat liver DNA polymerase by nitrosoureas and isocyanates. Cancer Res. 35 (1975) 1-5
28. Ishiguro K., Seow H.A., Penketh P.G., Shyam K., and Sartorelli A.C. Mode of action of the chloroethylating and carbamoylating moieties of the prodrug cloretazine. Mol. Cancer Ther. 5 (2006) 969-976
29. Kosa J.L., and Sweasy J.B. 3′-Azido-3′-deoxythymidine-resistant mutants of DNA polymerase beta identified by in vivo selection. J. Biol. Chem. 274 (1999) 3851-3858
30. de Levie R. Advanced Excel for Scientific Data Analysis. second ed. (2008), Oxford University Press, New York
31. Giles F., Thomas D., Garcia-Manero G., Faderl S., Cortes J., Verstovsek S., Ferrajoli A., Jeha S., Beran M., Koller C., Andreeff M., Cahill A., Clairmont C., Sznol M., and Kantarjian H. A phase I and pharmacokinetic study of VNP40101M, a novel sulfonylhydrazine alkylating agent, in patients with refractory leukemia. Clin. Cancer Res. 10 (2004) 2908-2917
32. Allinson S.L., Dianova I.I., and Dianov G.L. DNA polymerase beta is the major dRP lyase involved in repair of oxidative base lesions in DNA by mammalian cell extracts. EMBO J. 20 (2001) 6919-6926
33. Sobol R.W., Prasad R., Evenski A., Baker A., Yang X.P., Horton J.K., and Wilson S.H. The lyase activity of the DNA repair protein beta-polymerase protects from DNA-damage-induced cytotoxicity. Nature 405 (2000) 807-810
34. Beard W.A., Prasad R., and Wilson S.H. Activities and mechanism of DNA polymerase beta. Methods Enzymol. 408 (2006) 91-107