Can Drosophila melanogaster represent a model system for the detection of reproductive adverse drug reactions?

Avanesian, Agnesa; Semnani, Sahar; Jafari, Mahvash

doi:10.1016/j.drudis.2009.05.010

Cited by 32 publications

(19 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…1 Flies exhibit a short generation time and high fecundity and have a well-differentiated central nervous system, cardiac anatomy, malphigian tubules (mammalian kidney analogs), and fat body (mammalian adipose tissue analogs). [2][3][4][5][6][7] Also, the ease of inducing gene knockouts and mutagenesis has rendered D. melanogaster as a powerful model to pursue demographic studies on various metabolic disorders.…”

Section: Introductionmentioning

confidence: 99%

Effect of semolina-jaggery diet on survival and development ofDrosophila melanogaster

Chattopadhyay

James

Roy

et al. 2015

Fly

View full text Add to dashboard Cite

Drosophila melanogaster is an ideal model organism for developmental studies. This study tests the potential of semolina-jaggery (SJ) diet as a new formulation for bulk rearing of flies. Semolina and jaggery are organic products obtained from wheat endosperm and cane sugar, respectively. Semolina is a rich source of carbohydrates and protein. Jaggery has a high content of dietary sugars. Moreover, preparation of semolina jaggery diet is cost-effective and easy. Thus, the current study aimed to compare survival and developmental parameters of flies fed the SJ diet to flies fed the standard cornmeal-sugar-yeast (CSY) diet. SJ diet enhanced survival of flies without affecting fecundity; male flies showed increased resistance to starvation. A higher number of flies emerged at F 2 and F 3 generation when fed the SJ diet than when fed the control CSY diet. SJ diet did not increase fly body weight and lipid percentage. Therefore, SJ diet can be used for bulk rearing of healthy flies at par with the standard cornmeal-sugar-yeast diet.

show abstract

Section: Introductionmentioning

confidence: 99%

Effect of semolina-jaggery diet on survival and development ofDrosophila melanogaster

Chattopadhyay

James

Roy

et al. 2015

Fly

View full text Add to dashboard Cite

show abstract

“…We observed that many chemotherapy drugs have measurable effects on fecundity at doses orders of magnitude smaller than those required to cause death (Kislukhin et al 2012). In addition, D. melanogaster has been proposed as a model system for assessing potential toxic side effects influencing reproduction (Avanesian et al 2009). Similarities between the reproductive system in D. melanogaster and humans include overall similarity between female reproductive structures, conserved sexual development genes, and the existence of sex hormones (Avanesian et al 2009).…”

mentioning

confidence: 99%

“…In addition, D. melanogaster has been proposed as a model system for assessing potential toxic side effects influencing reproduction (Avanesian et al 2009). Similarities between the reproductive system in D. melanogaster and humans include overall similarity between female reproductive structures, conserved sexual development genes, and the existence of sex hormones (Avanesian et al 2009). In addition, chemotherapy drugs often target basal cell-level pathways, which often show one-to-one gene conservation between D. melanogaster and humans (Bier 2005), making D. melanogaster a powerful model for identifying candidate genes influencing chemotoxicity in humans.…”

mentioning

confidence: 99%

Using Drosophila melanogaster To Identify Chemotherapy Toxicity Genes

King

Kislukhin

Walters³

et al. 2014

Genetics

View full text Add to dashboard Cite

The severity of the toxic side effects of chemotherapy shows a great deal of interindividual variability, and much of this variation is likely genetically based. Simple DNA tests predictive of toxic side effects could revolutionize the way chemotherapy is carried out. Due to the challenges in identifying polymorphisms that affect toxicity in humans, we use Drosophila fecundity following oral exposure to carboplatin, gemcitabine and mitomycin C as a model system to identify naturally occurring DNA variants predictive of toxicity. We use the Drosophila Synthetic Population Resource (DSPR), a panel of recombinant inbred lines derived from a multiparent advanced intercross, to map quantitative trait loci affecting chemotoxicity. We identify two QTL each for carboplatin and gemcitabine toxicity and none for mitomycin. One QTL is associated with fly orthologs of a priori human carboplatin candidate genes ABCC2 and MSH2, and a second QTL is associated with fly orthologs of human gemcitabine candidate genes RRM2 and RRM2B. The third, a carboplatin QTL, is associated with a posteriori human orthologs from solute carrier family 7A, INPP4A&B, and NALCN. The fourth, a gemcitabine QTL that also affects methotrexate toxicity, is associated with human ortholog GPx4. Mapped QTL each explain a significant fraction of variation in toxicity, yet individual SNPs and transposable elements in the candidate gene regions fail to singly explain QTL peaks. Furthermore, estimates of founder haplotype effects are consistent with genes harboring several segregating functional alleles. We find little evidence for nonsynonymous SNPs explaining mapped QTL; thus it seems likely that standing variation in toxicity is due to regulatory alleles. CHEMOTHERAPEUTIC agents are among the most toxic medications administered to humans (Alley et al. 2002). The toxicity caused by these medications may become severe enough that patients are forced to adjust dosing or switch to a different chemotherapeutic medication, while the disease progresses. Although diet, medical history, age, and other environmental factors of the patient may explain a portion of the toxicity (Gajewski et al. 1989;Meirow and Nugent 2001; Rothenberg et al. 2003;Watters and McLeod 2003;Lee et al. 2005), we have shown that there is a significant genetic component governing the toxic effect of several drugs in Drosophila melanogaster (Kislukhin et al. 2012). Here we use the D. melanogaster model system to dissect the genetic basis of toxicity for three front-line chemotherapeutics: carboplatin, gemcitabine hydrochloride (gemcitabine), and mitomycin C.Carboplatin is a platinum-containing compound used primarily to treat ovarian cancer. It is also sometimes used to treat lung, breast, bladder, and endometrial cancer; head and neck cancer; cancer of the cervix and testicles; certain types of brain cancer; Wilms' tumor; neuroblastoma; and retinoblastoma (Wheate et al. 2010). Gemcitabine is an antimetabolite used primarily in combination with other chemotherapy drugs to treat ovarian...

show abstract

“…Although in vitro models provide valuable teratogenicity data, they cover all of the aspects of prenatal development; they also lack a placenta, which offers some protection for the developing organism in mammals, and so cannot determine the real fetal exposure (Avanesian et al, 2009;Van den Bulck et al, 2011). None of these in vitro methods can currently be regarded as a full replacement for existing in vivo studies; however they can be considered as a pre-screen strategy to prioritize xenobiotics for in vivo assessment, reducing and optimizing animal use in teratogenicity evaluation.…”

Section: Utility Of In Vitro Methodsmentioning

confidence: 99%

“…The zebrafish, a small freshwater fish (3 cm) offers several advantages for teratogenicity assessment including economic husbandry requirements, high fecundity and rapid ex utero development (Hill et al, 2005;Avanesian et al, 2009). The eggs remain transparent from fertilization up to and beyond pharyngulation when the tissues become dense and pigmentation is initiated.…”

Section: Embryos Of Lower Order Species Testmentioning

confidence: 99%

Review of current and “omics” methods for assessing the toxicity (genotoxicity, teratogenicity and nephrotoxicity) of herbal medicines and mushrooms

Ouédraogo

Baudoux

Stévigny

et al. 2012

Journal of Ethnopharmacology

124

View full text Add to dashboard Cite

show abstract

Can Drosophila melanogaster represent a model system for the detection of reproductive adverse drug reactions?

Cited by 32 publications

References 58 publications

Effect of semolina-jaggery diet on survival and development ofDrosophila melanogaster

Effect of semolina-jaggery diet on survival and development ofDrosophila melanogaster

Using Drosophila melanogaster To Identify Chemotherapy Toxicity Genes

Review of current and “omics” methods for assessing the toxicity (genotoxicity, teratogenicity and nephrotoxicity) of herbal medicines and mushrooms

Contact Info

Product

Resources

About