A new anticancer platinum compound, (-)-(R)-2-aminomethyl-pyrrolidine(1,1-cyclobutanedicarboxylato) platinum(II): DNA interstrand crosslinking, repair and lethal effects in normal human, Fanconi's anaemia and xeroderma pigmentosum cells.

Interstrand cross-linking, repair and lethal effects of (-)-(R)-2-aminomethylpyrrolidine(1,1-cyclobutanedicarboxylato++ +) platinum(II) (DWA2114R) were studied in normal human. Fanconi's anaemia (FA) and xeroderma pigmentosum group A (XPA) cells. Interstrand crosslinking by DWA2114R was slower...

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Main Authors:	Fujiwara, Y., Nakamura, M., Yokoo, S.
Format:	Online
Language:	English
Published:	1993
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1968491/

id	pubmed-1968491
recordtype	oai_dc
spelling	pubmed-19684912009-09-10 A new anticancer platinum compound, (-)-(R)-2-aminomethyl-pyrrolidine(1,1-cyclobutanedicarboxylato) platinum(II): DNA interstrand crosslinking, repair and lethal effects in normal human, Fanconi's anaemia and xeroderma pigmentosum cells. Fujiwara, Y. Nakamura, M. Yokoo, S. Research Article Interstrand cross-linking, repair and lethal effects of (-)-(R)-2-aminomethylpyrrolidine(1,1-cyclobutanedicarboxylato++ +) platinum(II) (DWA2114R) were studied in normal human. Fanconi's anaemia (FA) and xeroderma pigmentosum group A (XPA) cells. Interstrand crosslinking by DWA2114R was slower than that by cisplatin (CDDP), since DWA2114R produced mainly Pt(II)-monoadducts after 1 h treatment, followed by progressive interstrand crosslinking to a maximum 5 h post-incubation, while CDDP induced rapidly interstrand crosslinks in approximately 70% DNA during the 1 h treatment, followed by a approximately 30% residual increase. At the maximum rate, DWA2114R was 18 times less interstrand-crosslinking than CDDP on the 1 mM basis. FA cells were specifically defective in the first half-excision of DWA2114R and CDDP-induced Pt(II) interstrand crosslinks, but XPA cells were as proficient as normal cells (t1/2 = 5-7 h). On the contrary, XPA cells were deficient in excision repair of intrastrand crosslinks, but FA cells were normal. In clonogenic survival curves of all types of cells, mean lethal doses (Do) of DWA2114R were an order of magnitude greater than those of CDDP. FA cells were most (3.5 times) sensitive (Do = 25.1 +/- 0.96 microM) and XPA cells were 1.9 times more sensitive (Do = 47.1 +/- 0.17 microM) to DWA2114R than normal cells (Do = 87.6 +/- 5.65 microM). DWA2114R and carboplatin with a cyclobutanedicarboxylato group exhibited almost similar lethal effects on each of normal, FA and XPA strains. FA (Do = 3.44 +/- 0.44 microM) and XPA cells (Do = 3.84 +/- 0.17 microM) were similarly 3-fold more sensitive to CDDP than normal (Do = 9.97 +/- 0.15 microM). On the basis of a single lethal hit (Do), thus DWA2114R and carboplatin effectively killed more FA cells defective in interstrand crosslink repair than XPA cells defective in intrastrand crosslink repair. 1993-06 /pmc/articles/PMC1968491/ /pubmed/8512813 Text en
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Fujiwara, Y. Nakamura, M. Yokoo, S.
spellingShingle	Fujiwara, Y. Nakamura, M. Yokoo, S. A new anticancer platinum compound, (-)-(R)-2-aminomethyl-pyrrolidine(1,1-cyclobutanedicarboxylato) platinum(II): DNA interstrand crosslinking, repair and lethal effects in normal human, Fanconi's anaemia and xeroderma pigmentosum cells.
author_facet	Fujiwara, Y. Nakamura, M. Yokoo, S.
author_sort	Fujiwara, Y.
title	A new anticancer platinum compound, (-)-(R)-2-aminomethyl-pyrrolidine(1,1-cyclobutanedicarboxylato) platinum(II): DNA interstrand crosslinking, repair and lethal effects in normal human, Fanconi's anaemia and xeroderma pigmentosum cells.
title_short	A new anticancer platinum compound, (-)-(R)-2-aminomethyl-pyrrolidine(1,1-cyclobutanedicarboxylato) platinum(II): DNA interstrand crosslinking, repair and lethal effects in normal human, Fanconi's anaemia and xeroderma pigmentosum cells.
title_full	A new anticancer platinum compound, (-)-(R)-2-aminomethyl-pyrrolidine(1,1-cyclobutanedicarboxylato) platinum(II): DNA interstrand crosslinking, repair and lethal effects in normal human, Fanconi's anaemia and xeroderma pigmentosum cells.
title_fullStr	A new anticancer platinum compound, (-)-(R)-2-aminomethyl-pyrrolidine(1,1-cyclobutanedicarboxylato) platinum(II): DNA interstrand crosslinking, repair and lethal effects in normal human, Fanconi's anaemia and xeroderma pigmentosum cells.
title_full_unstemmed	A new anticancer platinum compound, (-)-(R)-2-aminomethyl-pyrrolidine(1,1-cyclobutanedicarboxylato) platinum(II): DNA interstrand crosslinking, repair and lethal effects in normal human, Fanconi's anaemia and xeroderma pigmentosum cells.
title_sort	new anticancer platinum compound, (-)-(r)-2-aminomethyl-pyrrolidine(1,1-cyclobutanedicarboxylato) platinum(ii): dna interstrand crosslinking, repair and lethal effects in normal human, fanconi's anaemia and xeroderma pigmentosum cells.
description	Interstrand cross-linking, repair and lethal effects of (-)-(R)-2-aminomethylpyrrolidine(1,1-cyclobutanedicarboxylato++ +) platinum(II) (DWA2114R) were studied in normal human. Fanconi's anaemia (FA) and xeroderma pigmentosum group A (XPA) cells. Interstrand crosslinking by DWA2114R was slower than that by cisplatin (CDDP), since DWA2114R produced mainly Pt(II)-monoadducts after 1 h treatment, followed by progressive interstrand crosslinking to a maximum 5 h post-incubation, while CDDP induced rapidly interstrand crosslinks in approximately 70% DNA during the 1 h treatment, followed by a approximately 30% residual increase. At the maximum rate, DWA2114R was 18 times less interstrand-crosslinking than CDDP on the 1 mM basis. FA cells were specifically defective in the first half-excision of DWA2114R and CDDP-induced Pt(II) interstrand crosslinks, but XPA cells were as proficient as normal cells (t1/2 = 5-7 h). On the contrary, XPA cells were deficient in excision repair of intrastrand crosslinks, but FA cells were normal. In clonogenic survival curves of all types of cells, mean lethal doses (Do) of DWA2114R were an order of magnitude greater than those of CDDP. FA cells were most (3.5 times) sensitive (Do = 25.1 +/- 0.96 microM) and XPA cells were 1.9 times more sensitive (Do = 47.1 +/- 0.17 microM) to DWA2114R than normal cells (Do = 87.6 +/- 5.65 microM). DWA2114R and carboplatin with a cyclobutanedicarboxylato group exhibited almost similar lethal effects on each of normal, FA and XPA strains. FA (Do = 3.44 +/- 0.44 microM) and XPA cells (Do = 3.84 +/- 0.17 microM) were similarly 3-fold more sensitive to CDDP than normal (Do = 9.97 +/- 0.15 microM). On the basis of a single lethal hit (Do), thus DWA2114R and carboplatin effectively killed more FA cells defective in interstrand crosslink repair than XPA cells defective in intrastrand crosslink repair.
publishDate	1993
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1968491/
_version_	1611399685826674688

A new anticancer platinum compound, (-)-(R)-2-aminomethyl-pyrrolidine(1,1-cyclobutanedicarboxylato) platinum(II): DNA interstrand crosslinking, repair and lethal effects in normal human, Fanconi's anaemia and xeroderma pigmentosum cells.

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