Determination of mitomycin C, 2,7-diaminomitosene, 1,2-cis- and 1,2-trans-1-hydroxy-2,7-diaminomitosene in tumour tissue by high-performance liquid chromatography

Cummings, Jeffrey L.; Chirrey, Linda; Willmott, N.; Halbert, Gavin; Smyth, John F.

doi:10.1016/0378-4347(93)80373-c

Cited by 22 publications

(10 citation statements)

References 19 publications

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“…5,[14][15][16][17] The toxicity of these degradants is unknown. These degradants have been recognized, but prior studies have not assessed the percentage increase of degredants over time.…”

Section: Discussionmentioning

confidence: 99%

The Degradation of Mitomycin C Under Various Storage Methods

Kinast

Akula

DeBarber

et al. 2016

Journal of Glaucoma

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“…5,[14][15][16][17] The toxicity of these degradants is unknown. These degradants have been recognized, but prior studies have not assessed the percentage increase of degredants over time.…”

Section: Discussionmentioning

confidence: 99%

The Degradation of Mitomycin C Under Various Storage Methods

Kinast

Akula

DeBarber

et al. 2016

Journal of Glaucoma

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“…The bifunctional DNA alkylator and cross-linker MC is converted by simple chemical or enzymatic reduction to 2,7-DAM. 10a,b,d,f-h This reaction is interesting mechanistically since it proves the intermediacy of quinone methide 7 in the reductive activation of MC (Scheme ). 10a,h, It also represents the major path of the reductive metabolism of MC in tumor cells and tissues . Evidence that 2,7-DAM may also act as a reductive DNA alkylator was first provided by Remers and his colleagues,12a reporting an irreversible association of the mitosene chromophore with DNA after incubation with 2,7-DAM and Na 2 S 2 O 4 .…”

Section: Discussionmentioning

confidence: 99%

“…We isolated the resulting single covalent adduct and determined its structure, mechanism of formation, and DNA sequence specificity. Formation of this adduct is also important in the biological context since 2,7-DAM is a major byproduct of the reductive activation process of MC (Scheme ) in cell-free systems 10a,b,g,h and in tumor tissues and cells 16b…”

mentioning

confidence: 99%

2,7-Diaminomitosene, a Monofunctional Mitomycin C Derivative, Alkylates DNA in the Major Groove. Structure and Base-Sequence Specificity of the DNA Adduct and Mechanism of the Alkylation

et al. 1996

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Reductive activation of the bifunctional alkylator and DNA cross-linking agent mitomycin C (MC) yields 2,7-diaminomitosene (2,7-DAM) as the major product of its activation both in cell-free systems and in vivo. 2,7-DAM lacks one of the alkylating functions of MC, the aziridine. We show that 2,7-DAM itself alkylates DNA monofunctionally upon reductive activation, to form a heat-labile adduct. A guanine-N7−2,7-DAM adduct was isolated from the drug−DNA complex upon heating. Nuclease digestion yielded this adduct both in the nucleoside (dG-2,7-DAM) and dinucleoside phosphate [d(GpG)-2,7-DAM] forms. The structures of all three forms were determined by LC−ESIMS and differential UV spectroscopy. The adduct is sequence-specific to guanines in (G) n tracts of DNA. A guanine-N7−2,7-DAM adduct in DNA was indirectly observed previously by Prakash et al. (Prakash, A. S.; Beall, H.; Ross, D.; Gibson, N. W. Biochemistry 1993, 32, 5518−5525). The results indicate that selective removal of the aziridine function of MC results in a switch from minor to major groove alkylation of DNA, and a switch of sequence specificity from guanines in CpG to guanines in (G) n tracts. They also show that the mitosene C-10 carbamate intrinsically reacts as an SN2 alkylating agent, specific to guanine-N7.

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“…The formation of the metabolites is pH-dependant. Moreover, the factors such as oxygen tension and level of free radicals can influence the formation of the metabolites [49].…”

Section: Mitomycin Cmentioning

confidence: 99%

“…for the quantification of mitomycins in various biological matrices [49][50][51][52][53][54][55][56][57][58][59]. Paroni et al described an ultra sensitive method for the determination of MMC in human plasma with the LLOQ of 0.5 ng/mL [57].…”

Section: Mitomycin Cmentioning

confidence: 99%

Ultrasensitive Bioanalytical Assays for Cytotoxic Drugs: Focus on Locally Administered Anti-Cancer Agents

Vainchtein¹,

Rosing²,

Schellens³

et al. 2008

TOACJ

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Local administration routes have been investigated to reduce the systemic toxicity and to increase the local efficacy of cytotoxic drugs. Some examples of local administration strategies are cutaneous, intraperitoneal, intrathecal and intravesical chemotherapy. When administered locally, high local drug concentrations can be achieved with increased local efficacy and, conditionally that only small amounts of drug are absorbed into the bloodstream, low systemic toxicity. Our main purpose is to make an inventory and to comment on the availability of ultrasensitive bioanalytical assays that could determine traces of the drugs that may have passed into the bloodstream, e.g. after local application, and which may lead to the systemic toxicity. We conclude that in the last years, multiple ultrasensitive assays have been designed capable to quantitatively determine very low levels of cytotoxic agents e.g. systemically reached after local administration. Most methods are based on the hyphenated liquid chromatography with tandem mass spectrometric detection.

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Determination of mitomycin C, 2,7-diaminomitosene, 1,2-cis- and 1,2-trans-1-hydroxy-2,7-diaminomitosene in tumour tissue by high-performance liquid chromatography

Cited by 22 publications

References 19 publications

The Degradation of Mitomycin C Under Various Storage Methods

The Degradation of Mitomycin C Under Various Storage Methods

2,7-Diaminomitosene, a Monofunctional Mitomycin C Derivative, Alkylates DNA in the Major Groove. Structure and Base-Sequence Specificity of the DNA Adduct and Mechanism of the Alkylation

Ultrasensitive Bioanalytical Assays for Cytotoxic Drugs: Focus on Locally Administered Anti-Cancer Agents

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