DNA alkylation and interstrand cross-linking by treosulfan

The anti-tumour drug treosulfan (L-threitol 1,4-bismethanesulphonate, Ovastat) is a prodrug for epoxy compounds by converting non-enzymatically to L-diepoxybutane via the corresponding monoepoxide under physiological conditions. The present study supports the hypothesis that this conversion of treos...

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Autores principales: Hartley, J A, O'Hare, C C, Baumgart, J
Formato: Texto
Lenguaje:English
Publicado: Nature Publishing Group 1999
Materias:
Short
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2362201/
https://www.ncbi.nlm.nih.gov/pubmed/9888467
http://dx.doi.org/10.1038/sj.bjc.6690043
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author Hartley, J A
O'Hare, C C
Baumgart, J
author_facet Hartley, J A
O'Hare, C C
Baumgart, J
author_sort Hartley, J A
collection PubMed
description The anti-tumour drug treosulfan (L-threitol 1,4-bismethanesulphonate, Ovastat) is a prodrug for epoxy compounds by converting non-enzymatically to L-diepoxybutane via the corresponding monoepoxide under physiological conditions. The present study supports the hypothesis that this conversion of treosulfan is required for cytotoxicity in vitro. DNA alkylation and interstrand cross-linking of plasmid DNA is observed after treosulfan treatment, but this is again produced via the epoxide species. Alkylation occurs at guanine bases with a sequence selectivity similar to other alkylating agents such as the nitrogen mustards. In treosulfan-treated K562 cells, cross-links form slowly, reaching a peak at approximately 24 h. Incubation of K562 cells with preformed epoxides shows faster and more efficient DNA cross-linking. © 1999 Cancer Research Campaign
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spelling pubmed-23622012009-09-10 DNA alkylation and interstrand cross-linking by treosulfan Hartley, J A O'Hare, C C Baumgart, J Br J Cancer Short The anti-tumour drug treosulfan (L-threitol 1,4-bismethanesulphonate, Ovastat) is a prodrug for epoxy compounds by converting non-enzymatically to L-diepoxybutane via the corresponding monoepoxide under physiological conditions. The present study supports the hypothesis that this conversion of treosulfan is required for cytotoxicity in vitro. DNA alkylation and interstrand cross-linking of plasmid DNA is observed after treosulfan treatment, but this is again produced via the epoxide species. Alkylation occurs at guanine bases with a sequence selectivity similar to other alkylating agents such as the nitrogen mustards. In treosulfan-treated K562 cells, cross-links form slowly, reaching a peak at approximately 24 h. Incubation of K562 cells with preformed epoxides shows faster and more efficient DNA cross-linking. © 1999 Cancer Research Campaign Nature Publishing Group 1999-01 /pmc/articles/PMC2362201/ /pubmed/9888467 http://dx.doi.org/10.1038/sj.bjc.6690043 Text en Copyright © 1999 Cancer Research Campaign https://creativecommons.org/licenses/by/4.0/This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material.If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/.
spellingShingle Short
Hartley, J A
O'Hare, C C
Baumgart, J
DNA alkylation and interstrand cross-linking by treosulfan
title DNA alkylation and interstrand cross-linking by treosulfan
title_full DNA alkylation and interstrand cross-linking by treosulfan
title_fullStr DNA alkylation and interstrand cross-linking by treosulfan
title_full_unstemmed DNA alkylation and interstrand cross-linking by treosulfan
title_short DNA alkylation and interstrand cross-linking by treosulfan
title_sort dna alkylation and interstrand cross-linking by treosulfan
topic Short
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2362201/
https://www.ncbi.nlm.nih.gov/pubmed/9888467
http://dx.doi.org/10.1038/sj.bjc.6690043
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