Bleomycin-induced strand-scission of DNA. Mechanism of deoxyribose cleavage.

Giloni, L; Takeshita, Masaru; Johnson, Francis; Iden, Charles R.; Grollman, Arthur P.

doi:10.1016/s0021-9258(19)68888-5

Cited by 398 publications

(182 citation statements)

References 38 publications

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“…The products ((l-A-(3-oxo-lpropenyl)thymine and other 1-or 9-A-(3-oxo-l-propenyl)pyrimidine and purine bases etc. shown in figure 3) of the reaction of the bleomycin-iron-0 2 complex with DNA were isolated by P. Grollman and M. Takeshita (Giloni et al 1981). These reaction products suggest that bleomycin-Fe3+--0 2H abstracts the hydrogen radical from the 4-CH of the 2-deoxyribose moiety of DNA and this is followed by the reactions resulting in DNA strand scission.…”

Section: -2mentioning

confidence: 96%

The Leeuwenhoek Lecture, 1982 - Studies of microbial products in rising to the challenge of curing cancer

Umezawa

1983

Proc. R. Soc. Lond. B.

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The author’s studies, with his collaborators, on antitumour antibiotics, low molecular mass immunity-enhancing compounds by microorganisms, and microbial products inhibiting the generation of cells that suppress immunity are described. Among about 50 antitumour antibiotics discovered, bleomycin has been used in cancer treatment. The complicated structures of bleomycin and its metal complexes were determined and totally synthesized. The fermentation and chemical methods for preparation of bleomycin analogues and derivatives were established, and, on the basis of action mechanisms, analogues with improved therapeutic activity were developed. Anthracycline antibiotics were also studied; aclacinomycin, effective against leukaemia, and 4´- O -tetrahydropyranyladriamycin (THP), which has strong therapeutic effects against various types of cancer, were developed. Among new antibiotics recently discovered, spergaulin is discussed. A unique screening method for finding microbial products that bind to cell surfaces was established, resulting in the discovery of bestatin, arphamenines, forphenicine, forphenicinol and ebelactones which enhance the action of cellular immunity. Bestatin has been studied in great detail, exhibiting favourable effects in randomization tests. The importance of compounds that can suppress the generation of suppressor cells is discussed. A new antitumour antibiotic, named oxanosine, and arphamenines, described above, were found to inhibit the generation of suppressor cells The contribution of antibacterial antibiotics to cancer treatment is also discussed. It is proposed that a combination treatment with chemotherapeutic agents, low molecular mass immunity-enhancing agents and compounds that inhibit the generation of suppressor cells will make a great contribution to cure cancer.

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Section: -2mentioning

confidence: 96%

The Leeuwenhoek Lecture, 1982 - Studies of microbial products in rising to the challenge of curing cancer

Umezawa

1983

Proc. R. Soc. Lond. B.

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“…The amino terminal tripeptide of Bleomycin molecule seemingly intercalates between guanine-cytosine base pairs of DNA. The opposite end of the Bleomycin peptide binds Fe(II) and serves as a ferrous oxidase, able to catalyze the reduction of molecular oxygen to superoxide or hydroxyl radicals responsible for DNA strand scission (Takeshita et al, 1978;Giloni et al, 1981). Recently, a new class of drugs is being developed -pyrazolo-triazoles that are DNA cleaving agents upon Chemical structures of DNA cleaving antibiotics photoactivation (Manfredini et al, 2000).…”

Section: Dna Cleaving Anticancer Drugsmentioning

confidence: 99%

Chromatin as a Target for the DNA-Binding Anticancer Drugs

Majumder

Pradhan

Devi

et al. 2007

Subcellular Biochemistry

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Chemotherapy has been a major approach to treat cancer. Both constituents of chromatin, chromosomal DNA and the associated chromosomal histone proteins are the molecular targets of the anticancer drugs. Small DNA binding ligands, which inhibit enzymatic processes with DNA substrate, are well known in cancer chemotherapy. These drugs inhibit the polymerase and topoisomerase activity. With the advent in the knowledge of chromatin chemistry and biology, attempts have shifted from studies of the structural basis of the association of these drugs or small ligands (with the potential of drugs) with DNA to their association with chromatin and nucleosome. These drugs often inhibit the expression of specific genes leading to a series of biochemical events. An overview will be given about the latest understanding of the molecular basis of their action. We shall restrict to those drugs, synthetic or natural, whose prime cellular targets are so far known to be chromosomal DNA

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“…DNA damage by bleomycin requires Fe(II) [30]. Bleomycin-damaged DNA itself is a poor template-primer for DNA synthesis by Klenow polymerase [19,23], because 3' ends of the damaged DNA are not free but phosphoglycolated [30,31].…”

Section: Priming Activi~ O[ the 30 Kda Enzyme [Or Dna Synthesis On Bl...mentioning

confidence: 99%

Purification and characterization of an AP endonuclease/DNA 3′repair diesterase from mouse ascites sarcoma cells

Sarker

Watanabe

Akiyama

et al. 1995

Biochimica et Biophysica Acta (BBA) - General Subjects

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Bleomycin-induced strand-scission of DNA. Mechanism of deoxyribose cleavage.

Cited by 398 publications

References 38 publications

The Leeuwenhoek Lecture, 1982 - Studies of microbial products in rising to the challenge of curing cancer

The Leeuwenhoek Lecture, 1982 - Studies of microbial products in rising to the challenge of curing cancer

Chromatin as a Target for the DNA-Binding Anticancer Drugs

Purification and characterization of an AP endonuclease/DNA 3′repair diesterase from mouse ascites sarcoma cells

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