Mitomycin C: small, fast and deadly (but very selective)

Tomasz, Maria

doi:10.1016/1074-5521(95)90120-5

Cited by 530 publications

(396 citation statements)

References 25 publications

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“…DNA damages and defective DNA repairs cause SCEs (Bozkurt et al 2003). In accordance with our finding, cellular toxicity after MMC exposure may occur from MMC-induced insults such as the generation of free radicals, DNA monoadducts, and SCE formations; however, the most significant effects are due to the accumulation of covalent DNA interstrand cross-links (Tomasz 1995;Liao et al 2012;Rencuzogullari et al 2012).…”

Section: Discussionsupporting

confidence: 92%

Xanthoria elegans (Link) (lichen) extract counteracts DNA damage and oxidative stress of mitomycin C in human lymphocytes

2012

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Several lichen species have been used for medicinal purposes throughout the ages, and they are reported to be effective in the treatment of different disorders including ulcer and cancer. It is revealed that lichens may be easily accessible sources of natural drugs and possible food supplements after their safety evaluations. The main objective in this study was to evaluate the roles of aqueous extracts of Xanthoria elegans (at 25, 50 and 100 lg/ml) upon mitomycin C (MMC; at 10 -7 M) induced genotoxic and oxidative damages in cultured human lymphocytes. X. elegans were collected from the Erzurum and Artvin provinces (in Turkey) during August 2010. After the application of MMC and X. elegans extract (XEE), separate and together, human whole blood cultures were assessed by four genotoxicity end-points including chromosomal aberration, micronucleus, sister chromatid exchange (SCE) and 8-oxo-2-deoxyguanosine (8-OHdG) assays. In addition, biochemical parameters [total antioxidant capacity (TAC) and total oxidative stress (TOS)] were examined to determine oxidative effects. According to our results, the frequencies of cytogenetic endpoints and 8-OH-dG levels were significantly increased by MMC compared with controls in human peripheral lymphocytes. MMC caused oxidative stress by altering TAC and TOS levels. On the contrary, XEE led to increases of TAC level without changing TOS level. XEE had no genotoxic effect. Furthermore, our findings revealed that MMC induced increases in the mean frequencies of four genotoxic indices were diminished by XEE in dose dependent manner, indicating its protective role towards cells from MMC exerted injury. In conclusion, the results obtained in the present study indicate for the first time that XEE is a potential source of natural antigenotoxicants.

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Section: Discussionsupporting

confidence: 92%

Xanthoria elegans (Link) (lichen) extract counteracts DNA damage and oxidative stress of mitomycin C in human lymphocytes

2012

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“…This also holds true for exposure to the anticancer drugs analyzed in the present study. Phosphotriester adducts constitute the most frequent alterations by CPP (21), alkylated monoadducts and cross-linked adducts dominate in the spectrum of MMC-damaged sites (22), and PCH metabolites inhibit DNA polymerase and also react directly with DNA (23). Thus, it appears that relatively high-dose acute exposure to various germ-line mutagens can result in transgenerational instability manifesting in the offspring.…”

Section: Discussionmentioning

confidence: 99%

Exposure to anticancer drugs can result in transgenerational genomic instability in mice

Glen

Dubrova

2012

Proc. Natl. Acad. Sci. U.S.A.

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The genetic effects of human exposure to anticancer drugs remain poorly understood. To establish whether exposure to anticancer drugs can result not only in mutation induction in the germ line of treated animals, but also in altered mutation rates in their offspring, we evaluated mutation rates in the offspring of male mice treated with three commonly used chemotherapeutic agents: cyclophosphamide, mitomycin C, and procarbazine. The doses of paternal exposure were approximately equivalent to those used clinically. Using single-molecule PCR, the frequency of mutation at the mouse expanded simple tandem repeat locus Ms6-hm was established in DNA samples extracted from sperm and bone marrow of the offspring of treated males. After paternal exposure to any one of these three drugs, expanded simple tandem repeat mutation frequencies were significantly elevated in the germ line (sperm) and bone marrow of their offspring. This observed transgenerational instability was attributed to elevated mutation rates at the alleles derived from both the exposed fathers and from the nonexposed mothers, thus implying a genome-wide destabilization. Our results suggest that paternal exposure to a wide variety of mutagens can result in transgenerational instability manifesting in their offspring. Our data also raise important issues concerning delayed transgenerational effects in the children of survivors of anticancer therapy.epigenetic | genetic risk

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“…7) is a potent cytotoxin in clinical use against a variety of cancers. 66 Its mode of action is DNA alkylation and cross-linking. 67 Reductive activation 68 of mitomycin delivers the hydroquinone, which leads to methanol elimination and an aziridine ring-opening to give an extended quinone-methide electrophile.…”

Section: Natural Products That Covalently Modify Nucleobasesmentioning

confidence: 99%

Properties and reactivity of nucleic acids relevant to epigenomics, transcriptomics, and therapeutics

2016

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Developments in epigenomics, toxicology, and therapeutic nucleic acids all rely on a precise understanding of nucleic acid properties and chemical reactivity. In this review we discuss the properties and chemical reactivity of each nucleobase and attempt to provide some general principles for nucleic acid targeting or engineering. For adenine-thymine and guaninecytosine base pairs, we review recent quantum chemical estimates of their Watson-Crick interaction energy, - stacking energies, as well as the nuclear quantum effects on tautomerism. Reactions that target nucleobases have been crucial in the development of new sequencing technologies and we believe further developments in nucleic acid chemistry will be required to deconstruct the enormously complex transcriptome.

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Mitomycin C: small, fast and deadly (but very selective)

Cited by 530 publications

References 25 publications

Xanthoria elegans (Link) (lichen) extract counteracts DNA damage and oxidative stress of mitomycin C in human lymphocytes

Xanthoria elegans (Link) (lichen) extract counteracts DNA damage and oxidative stress of mitomycin C in human lymphocytes

Exposure to anticancer drugs can result in transgenerational genomic instability in mice

Properties and reactivity of nucleic acids relevant to epigenomics, transcriptomics, and therapeutics

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