Etoposide

Henwood, Julian M.; Brogden, Rex N.

doi:10.2165/00003495-199039030-00008

Cited by 107 publications

(34 citation statements)

References 234 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…commonly used agents in cancer chemotherapy (1,2) and has improved significantly the treatment of leukemia, lymphomas, and many solid tumors, including testicular and ovarian cancers (3). However, evidence is accumulating that ET is genotoxic (4)(5)(6), and that it can induce secondary tumors (7) and impair fertility (6).…”

mentioning

confidence: 99%

Etoposide induces heritable chromosomal aberrations and aneuploidy during male meiosis in the mouse

Marchetti

Bishop

Lowe

et al. 2001

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

View full text Add to dashboard Cite

Etoposide, a topoisomerase II inhibitor widely used in cancer therapy, is suspected of inducing secondary tumors and affecting the genetic constitution of germ cells. A better understanding of the potential heritable risk of etoposide is needed to provide sound genetic counseling to cancer patients treated with this drug in their reproductive years. We used a mouse model to investigate the effects of clinical doses of etoposide on the induction of chromosomal abnormalities in spermatocytes and their transmission to zygotes by using a combination of chromosome painting and 4 ,6-diamidino-2-phenylindole staining. High frequencies of chromosomal aberrations were detected in spermatocytes within 64 h after treatment when over 30% of the metaphases analyzed had structural aberrations (P < 0.01). Significant increases in the percentages of zygotic metaphases with structural aberrations were found only for matings that sampled treated pachytene (28-fold, P < 0.0001) and preleptotene spermatocytes (13-fold, P < 0.001). Etoposide induced mostly acentric fragments and deletions, types of aberrations expected to result in embryonic lethality, because they represent loss of genetic material. Chromosomal exchanges were rare. Etoposide treatment of pachytene cells induced aneuploidy in both spermatocytes (18-fold, P < 0.01) and zygotes (8-fold, P < 0.05). We know of no other report of an agent for which paternal exposure leads to an increased incidence of aneuploidy in the offspring. Thus, we found that therapeutic doses of etoposide affect primarily meiotic germ cells, producing unstable structural aberrations and aneuploidy, effects that are transmitted to the progeny. This finding suggests that individuals who undergo chemotherapy with etoposide may be at a higher risk for abnormal reproductive outcomes especially within the 2 months after chemotherapy.

show abstract

mentioning

confidence: 99%

Etoposide induces heritable chromosomal aberrations and aneuploidy during male meiosis in the mouse

Marchetti

Bishop

Lowe

et al. 2001

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

View full text Add to dashboard Cite

show abstract

“…The chemotherapeutic drug etoposide is used as a salvage treatment for advanced stage breast cancer and causes DNA damage by stabilization of DNA topoisomerase II. Etoposide stabilizes the topoisomerase II –DNA covalent complex impairing the strand-rejoining activity of the enzyme causing double stranded DNA breaks to persist instead of being repaired [3]. Etoposide can delay progression of the cell cycle through the late S or early G2 phase but has no effect on tubulin assembly [3].…”

Section: Introductionmentioning

confidence: 99%

“…Etoposide stabilizes the topoisomerase II –DNA covalent complex impairing the strand-rejoining activity of the enzyme causing double stranded DNA breaks to persist instead of being repaired [3]. Etoposide can delay progression of the cell cycle through the late S or early G2 phase but has no effect on tubulin assembly [3]. As a single agent, oral etoposide response rate for breast cancer was found to be around 35% [4] and the mean bioavailability of orally administered etoposide is approximately 50% [3].…”

Section: Introductionmentioning

confidence: 99%

Differential Gene and MicroRNA Expression between Etoposide Resistant and Etoposide Sensitive MCF7 Breast Cancer Cell Lines

Moitra

Limpert

et al. 2012

PLoS ONE

View full text Add to dashboard Cite

show abstract

“…(1)) is a DNA topoisomerase II poison that is widely used as an antineoplastic agent. It is highly active against many adult and pediatric solid tumors and leukemias [1]. However, anticancer treatment with etoposide led to a form of secondary leukemia characterized by balanced chromosomal translocations as a treatment complication [2][3][4][5].…”

Section: Introductionmentioning

confidence: 99%

“…) 1. H-1 H two-dimensional COSY NMR spectrum of etoposide-OH (400 MHz, in MeOH-d 4 ) and the structure of etoposide-…”

mentioning

confidence: 99%

Characterization of an Etoposide-Glutathione Conjugate Derived from Metabolic Activation by Human Cytochrome P450

Zheng¹,

Pang²,

Oe³

et al. 2006

CDM

View full text Add to dashboard Cite

Etoposide (VP-16), a DNA topoisomerase II poison widely used as an antineoplastic agent is also known to cause leukemia. One of its major metabolic pathways involves O-demethylation to etoposide catechol (etoposide-OH) by cytochrome P450 3A4 (CYP3A4). The catechol metabolite can undergo sequential one- and two-electron oxidations to form etoposide semi-quinone (etoposide-SQ) and etoposide quinone (etoposide-Q), respectively, which have both been implicated as cytotoxic metabolites. However, etoposide-Q is known to react with glutathione (GSH), which can protect DNA from oxidative damage by this reactive metabolite. In this study, etoposide-Q was reacted with GSH and the two etoposide-GSH conjugates were characterized. The major conjugate was etoposide-OH-6'-SG and the minor product was etoposide-OH-2'-SG. Etoposide-OH-6'-SG, which arose from Michael addition of GSH to etoposide-Q, was characterized by mass spectrometry and 2-D NMR. It was identified as the sole product from in vitro metabolism experiments using recombinant human CYP3A4 or liver microsomes incubated with etoposide in the presence of GSH. Etoposide-OH-6'-SG was also detected from incubations of etoposide-OH and GSH alone. Therefore, the presence of etoposide-OH, which can be formed from etoposide metabolism by CYP3A4, is essential for formation of the GSH conjugate. The oxidation of etoposide-OH to a quinone intermediate is likely the precursor in the formation of etoposide-OH-6'-SG.

show abstract

Etoposide

Cited by 107 publications

References 234 publications

Etoposide induces heritable chromosomal aberrations and aneuploidy during male meiosis in the mouse

Etoposide induces heritable chromosomal aberrations and aneuploidy during male meiosis in the mouse

Differential Gene and MicroRNA Expression between Etoposide Resistant and Etoposide Sensitive MCF7 Breast Cancer Cell Lines

Characterization of an Etoposide-Glutathione Conjugate Derived from Metabolic Activation by Human Cytochrome P450

Contact Info

Product

Resources

About