The Walker 256 carcinoma: a cell type inherently sensitive only to those difunctional agents that can form DNA interstrand crosslinks

Knox, Richard J.; Lydall, David; Friedlos, Frank; Basham, Connie; Rawlings, Christopher J.; Roberts, J. J.

doi:10.1016/0921-8777(91)90026-l

Cited by 21 publications

(15 citation statements)

References 28 publications

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“…Both Walker-sensitive and -resistant cells express large amounts of DT-D (Knox et al, 1991), an enzyme shown previously to metabolize E09 (Bailey et al, 1992;Walton et al, 1991.…”

Section: Discussionmentioning

confidence: 96%

“…A resistant subline, designated Walker resistant, arose as a result of continual exposure to chlorambucil in vitro (Knox et al, 1991). A range of difunctional alkylating agents that are capable of inducing DNA interstrand cross-links are particularly toxic towards the Walker-sensitive cells but are much less active against Walker-resistant cells (Knox et al, 1991).…”

Section: Discussionmentioning

confidence: 99%

“…The sensitivity of both rat Walker-sensitive and -resistant cells towards E09 was determined by clonogenic assay as described previously (Knox et al, 1991). Drug was dissolved in dimethyl sulphoxide (DMSO; < 1% final concentration) and treatment was for 2 h at 37°C.…”

Section: Clonogenic Assaymentioning

confidence: 99%

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Involvement of DT-diaphorase (EC 1.6.99.2) in the DNA cross-linking and sequence selectivity of the bioreductive anti-tumour agent EO9

Bailey¹,

Wyatt²,

Friedlos³

et al. 1997

Br J Cancer

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Summary The chemistry of the mitomycin C-related drug indoloquinone E09 would suggest that its mechanism of action is likely to involve DNA damage after reductive activation. The ability of this agent to induce DNA damage in intact cells has been examined using alkaline filter elution. After treatment with pharmacologically relevant concentrations of E09, both DNA strand breaks and interstrand cross-links were detected in rat Walker tumour cells and human HT29 colon carcinoma cells. These cell lines express relatively high levels of DT-diaphorase (NAD(P)H: quinone acceptor oxidoreductase), which is believed to be involved in E09 activation. The extent of DNA damage was increased by approximately 30-fold under hypoxia in BE colon carcinoma cells that express non-functional DT-diaphorase, but this dramatic hypoxia enhancement was not seen in HT-29 cells. These data are consistent with cytotoxicity studies that indicate that DT-diaphorase appears to be important in E09 activation under aerobic conditions, but other enzymes may be more relevant under hypoxia. The involvement of DTdiaphorase in DNA damage induction was further investigated using cell-free assays. DNA cross-links were detectable in plasmid DNA coincubated with E09, cofactor and DT-diaphorase but not in the absence of this enzyme. In contrast, using a Taq polymerase stop assay, monofunctional alkylation was detected in plasmid DNA without metabolic activation, although the sequence selectivity was altered after reduction catalysed by DT-diaphorase.

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“…Both Walker-sensitive and -resistant cells express large amounts of DT-D (Knox et al, 1991), an enzyme shown previously to metabolize E09 (Bailey et al, 1992;Walton et al, 1991.…”

Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

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Involvement of DT-diaphorase (EC 1.6.99.2) in the DNA cross-linking and sequence selectivity of the bioreductive anti-tumour agent EO9

Bailey¹,

Wyatt²,

Friedlos³

et al. 1997

Br J Cancer

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“…It has been well documented that substantial variation exists in the ability of different organisms (and different tissues within these organisms) to repair ICLs [Lawley and Brookes, 1968;Knox et al, 1991;Lawley and Phillips, 1996]. This variation is likely due, at least in part, to differences in the types of repair pathways used and in their relative robustness in different organisms.…”

mentioning

confidence: 97%

Strategies for DNA interstrand crosslink repair: Insights from worms, flies, frogs, and slime molds

McVey

2010

Environ and Mol Mutagen

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DNA interstrand crosslinks (ICLs) are complex lesions that covalently link both strands of the DNA double helix and impede essential cellular processes such as DNA replication and transcription. Recent studies suggest that multiple repair pathways are involved in their removal. Elegant genetic analysis has demonstrated that at least three distinct sets of pathways cooperate in the repair and/or bypass of ICLs in budding yeast. Although the mechanisms of ICL repair in mammals appear similar to those in yeast, important differences have been documented. In addition, mammalian crosslink repair requires other repair factors, such as the Fanconi anemia proteins, whose functions are poorly understood. Because many of these proteins are conserved in simpler metazoans, nonmammalian models have become attractive systems for studying the function(s) of key crosslink repair factors. This review discusses the contributions that various model organisms have made to the field of ICL repair. Specifically, it highlights how studies performed with C. elegans, Drosophila, Xenopus, and the social amoeba Dictyostelium serve to complement those from bacteria, yeast, and mammals. Together, these investigations have revealed that although the underlying themes of ICL repair are largely conserved, the complement of DNA repair proteins utilized and the ways in which each of the proteins is used can vary substantially between different organisms.

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“…n-Hexane extracts (where lanosterol is of a specifically strong effect) of Inonotus are able to stop the neoplastic process in Walker 256 carcinosarcoma cells [26], MCF -7 human mammary adenocarcinoma cells [27], P 388 leukemic cells. The components of the anti-tumor effect also include the ability to inhibit the inflammatory process.…”

Section: Inonotus Obliquusmentioning

confidence: 99%

Medicinal properties of fungi occurring on Betula sp. trees. A review

Smolibowska

Szymański

2016

Herba Polonica

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S u m m a r yThe article presents the chemical costituents and pharmacological properties of polyporoid fungi found on birch, namely Piptoporus betulinus, Inonotus obliquus, Lenzites betulina, Fomes fomentarius, and Trametes versicolor. The in vitro and in vivo studies on the effect of different extracts from above-mentioned fungi on the human organism shown anti-cancer, anti-inflammatory, antiviral, antibacterial and immunostimulant activity, conditioned by the presence of such compounds as polysaccharides, polyphenols or terpenes. These fungi are commonly found in Poland and may superbly compete with Ganoderma lucidum (Reishi) or Lentinula edodes (Shitake) used in Asia for medicinal purposes.

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The Walker 256 carcinoma: a cell type inherently sensitive only to those difunctional agents that can form DNA interstrand crosslinks

Cited by 21 publications

References 28 publications

Involvement of DT-diaphorase (EC 1.6.99.2) in the DNA cross-linking and sequence selectivity of the bioreductive anti-tumour agent EO9

Involvement of DT-diaphorase (EC 1.6.99.2) in the DNA cross-linking and sequence selectivity of the bioreductive anti-tumour agent EO9

Strategies for DNA interstrand crosslink repair: Insights from worms, flies, frogs, and slime molds

Medicinal properties of fungi occurring on Betula sp. trees. A review

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