COMPARISON OF TERATOGENIC CHEMICALS IN THE RAT AND CHICK EMBRYOS

PEDIATRICS ◽  
1957 ◽  
Vol 19 (4) ◽  
pp. 701-714
Author(s):  
M. Lois Murphy ◽  
C. P. Dagg ◽  
David A. Karnofsky

THE CHICK EMBRYO is used widely in studying drugs for teratogenic activity. Chemicals, which have been injected at the same period of incubation of the chick embryo, may produce separate and characteristic patterns of developmental abnormalities. The effects of many drugs, such as insulin, azaserine, sulfanilamide, 4-aminopteroyl glutamic acid, 8-azaguanine, physostigmine, thallium, lead, boric acid and cortisone, have been reviewed. The chick embryo in the egg is an isolated and independent system, whereas mammalian embryos are usually intimately involved with the maternal host which may detoxify, excrete or otherwise protect the fetus against noxious chemicals. It was, therefore, of interest to determine the effects of drugs, teratogenic in the chick embryo, on the mammalian fetus. The rat was selected because of its availability and because there is considerable information on rat embryology and teratology. Because some drugs, apparently inactive in the chick embryo, have produced consistent developmental abnormalities in the rat fetus, the pregnant rat also has been used for the initial study of selected compounds. The objectives of these studies were: 1) to determine and compare the teratogenic action of drugs on the chick and rat embryos; 2) to determine the consistency and specificity of action of each drug; 3) to determine the relation between the time during gestation when a drug is introduced and the occurrence of specific abnormalities; 4) to determine the relationship of the dose of a drug toxic to the mother, the dose toxic to the embryo, and the dose producing consistent developmental defects, and 5) to detect compounds which protect the embryo from the teratogenic action of a chemical.

2021 ◽  
Author(s):  
Steven Fanara ◽  
Marie Schloesser ◽  
Marc Hanikenne ◽  
Patrick Motte

The plant SR (serine/arginine-rich) splicing factor SR45 plays important roles in several biological processes, such as splicing, DNA methylation, innate immunity, glucose regulation and ABA signaling. A homozygous Arabidopsis sr45-1 null mutant is viable, but exhibits diverse phenotypic alterations, including delayed root development, late flowering, shorter siliques with fewer seeds, narrower leaves and petals, and unusual numbers of floral organs. Here, we report that the sr45-1 mutant presents an unexpected constitutive iron deficiency phenotype characterized by altered metal distribution in the plant. RNA-Sequencing highlighted severe perturbations in metal homeostasis, phenylpropanoid pathway, oxidative stress responses, and reproductive development. Ionomic quantification and histochemical staining revealed strong iron accumulation in the sr45-1 root tissues accompanied by an iron starvation in aerial parts. We showed that some sr45-1 developmental abnormalities can be complemented by exogenous iron supply. Our findings provide new insight into the molecular mechanisms governing the phenotypes of the sr45-1 mutant.


Development ◽  
1956 ◽  
Vol 4 (2) ◽  
pp. 110-118
Author(s):  
C. H. Waddington ◽  
M. M. Perry

Considerable interest has been aroused by the report of Gillman, Gilbert, Gillman, & Spence (1948) that the vital dye trypan blue when injected into the pregnant rat brings about the appearance of various abnormalities in the offspring. The mammal embryo is notoriously difficult to attack experimentally, and trypan blue therefore seems to provide a valuable tool which, moreover, might throw light on the mechanisms of the important effects which are known in some cases to be produced on the foetus by pathological states in the mother. Further studies on the effects of injected trypan blue on mammalian embryos have therefore been made by Hamburgh (1952, 1954), Waddington & Carter (1952, 1953), and Murakami and his collaborators (1952, 1954), all of whom worked on the mouse, and by Harm (1954) who studied the rabbit. All these authors agree, on the whole, in the type of results which they have obtained, although there are some minor differences between their reports which will be considered later.


2013 ◽  
Vol 210 (12) ◽  
pp. 2641-2659 ◽  
Author(s):  
Omar Abdel-Wahab ◽  
Jie Gao ◽  
Mazhar Adli ◽  
Anwesha Dey ◽  
Thomas Trimarchi ◽  
...  

Somatic Addition of Sex Combs Like 1 (ASXL1) mutations occur in 10–30% of patients with myeloid malignancies, most commonly in myelodysplastic syndromes (MDSs), and are associated with adverse outcome. Germline ASXL1 mutations occur in patients with Bohring-Opitz syndrome. Here, we show that constitutive loss of Asxl1 results in developmental abnormalities, including anophthalmia, microcephaly, cleft palates, and mandibular malformations. In contrast, hematopoietic-specific deletion of Asxl1 results in progressive, multilineage cytopenias and dysplasia in the context of increased numbers of hematopoietic stem/progenitor cells, characteristic features of human MDS. Serial transplantation of Asxl1-null hematopoietic cells results in a lethal myeloid disorder at a shorter latency than primary Asxl1 knockout (KO) mice. Asxl1 deletion reduces hematopoietic stem cell self-renewal, which is restored by concomitant deletion of Tet2, a gene commonly co-mutated with ASXL1 in MDS patients. Moreover, compound Asxl1/Tet2 deletion results in an MDS phenotype with hastened death compared with single-gene KO mice. Asxl1 loss results in a global reduction of H3K27 trimethylation and dysregulated expression of known regulators of hematopoiesis. RNA-Seq/ChIP-Seq analyses of Asxl1 in hematopoietic cells identify a subset of differentially expressed genes as direct targets of Asxl1. These findings underscore the importance of Asxl1 in Polycomb group function, development, and hematopoiesis.


2001 ◽  
Vol 21 (24) ◽  
pp. 8651-8656 ◽  
Author(s):  
Sung-Keun Lee ◽  
Sung-Lim Yu ◽  
Louise Prakash ◽  
Satya Prakash

ABSTRACT Mutations in the human CSB gene cause Cockayne syndrome (CS). In addition to increased photosensitivity, CS patients suffer from severe developmental abnormalities, including growth retardation and mental retardation. Whereas a deficiency in the preferential repair of UV lesions from the transcribed strand accounts for the increased photosensitivity of CS patients, the reason for developmental defects in these individuals has remained unclear. Here we provide in vivo evidence for a role of RAD26, the counterpart of the CSB gene in Saccharomyces cerevisiae, in transcription elongation by RNA polymerase II, and in addition we show that under conditions requiring rapid synthesis of new mRNAs, growth is considerably reduced in cells lackingRAD26. These findings implicate a role for CSB in transcription elongation, and they strongly suggest that impaired transcription elongation is the underlying cause of the developmental problems in CS patients.


2018 ◽  
Vol 18 (1) ◽  
pp. 73-82
Author(s):  
Firman Edigan ◽  
Deny Pratama Putra

[ID] PT PLN Rayon Tembilahan adalah perusahaan yang bergerak di bidang penyediaan tenaga listrik, pada penelitian awal terdapat pekerja pada shift siang masih banyak pekerja yang tidak menggunakan APD dengan lengkap sesuai dengan bagian pekerjaanya. Tujuan penelitian ini untuk mengetahui hubungan pengetahuan pekerja, kondisi lingkungan, ketersediaan sarana, pengawasan terhadap penggunaan APD pada pekerja teknisi mesin di PT PLN Rayon Tembilahan. Metode penelitian yang digunakan adalah penelitian kuantitatif dengan desain penelitian Cross Sectional. Sampel dalam penelitian ini menggunakan total sampling dimana pekerja teknisi mesin di PT PLN Rayon Tembilahan yang berjumlah 35 orang. Analisis data secara univariat dan bivariat dengan uji-square. Hasil penelitian yang diperoleh tidak ada hubungan pengetahuan dengan penggunaan APD dengan nilai p=0,899, adanya hubungan kondisi lingkungan dengan penggunaan APD dengan nilai p=0,022 dan diperoleh nilai OR=8,500, adanya hubungan sarana prasarana  dengan penggunaan APD dengan nilai p=0,031 dan diperoleh nilai OR=6,857, tidak ada hubungan pengawasan dengan penggunaan APD dengan nilai p=0,854 dan diperoleh nilai OR=1,429. Diharapkan kepada pihak PLN Rayon Tembilahan agar memperihatikan kondisi lingkungan kerja  dan bisa melengkapi sarana prasarana untuk pekerja agar dapat mengurangi resiko terhindar dari kecelakaan kerja. [EN] PT PLN Rayon Tembilahan is a company in the provision of electric power, In the initial study there are workers in the afternoon shift there are still many workers who do not use the complete PPE related with their work, the purpose of this study to determine the relationship of worker knowledge, environmental conditions, the availability of facilities, supervision of the use of PPE on workers in the engine technician PT PLN Rayon Tembilahan. The research method used is quantitative research with Cross Sectional research design. The sample in this research use total sampling where machine technician workers in PT PLN Rayon Tembilahan which amounted to 35 person. Univariate and bivariate data analysis with square test. The result of this research is no correlation with the use of PPE with p = 0,899, there is relation of environmental condition with PPE usage with p value = 0,022 and obtained value OR = 8,500, there is correlation of facility of infrastructure by using PPE with p value = 0,031 and Value OR = 6.857, there is no relationship of supervision with the use of PPE with the value p = 0.854 and obtained the value OR = 1.429. It is expected to PLN Rayon Tembilahan to envisage the condition of the work environment and can equip the infrastructure for workers to reduce the risk of avoidance of work accident.  


2011 ◽  
Vol 22 (6) ◽  
pp. 806-816 ◽  
Author(s):  
Neeraj Sharma ◽  
Zachary A. Kosan ◽  
Jannese E. Stallworth ◽  
Nicolas F. Berbari ◽  
Bradley K. Yoder

The primary cilium is an evolutionarily conserved dynamic organelle important for regulating numerous signaling pathways, and, as such, mutations disrupting ciliogenesis result in a variety of developmental abnormalities and postnatal disorders. The length of the cilium is regulated by the cell through largely unknown mechanisms. Normal cilia length is important, as either shortened or elongated cilia have been associated with disease and developmental defects. Here we explore the importance of cytoskeletal dynamics in regulating cilia length. Using pharmacological approaches in different cell types, we demonstrate that actin depolymerization or stabilization and protein kinase A activation result in a rapid elongation of the primary cilium. The effects of pharmacological agents on cilia length are associated with a subsequent increase in soluble tubulin levels and can be impaired by depletion of soluble tubulin with taxol. In addition, subtle nocodazole treatment was able to induce ciliogenesis under conditions in which cilia are not normally formed and also increases cilia length on cells that have already established cilia. Together these data indicate that cilia length can be regulated through changes in either the actin or microtubule network and implicate a possible role for soluble tubulin levels in cilia length control.


2002 ◽  
Vol 22 (20) ◽  
pp. 7204-7216 ◽  
Author(s):  
Irina Lagutina ◽  
Simon J. Conway ◽  
Jack Sublett ◽  
Gerard C. Grosveld

ABSTRACT Alveolar rhabdomyosarcoma is a pediatric disease specified by the recurrent chromosome translocations t(2;13) and t(1;13). These translocations result in the formation of the PAX3-FKHR and PAX7-FKHR fusion genes, which are thought to play a causal role in the genesis of this disease. Although PAX3-FKHR exhibits transforming activity in immortalized fibroblast cell lines, a direct role of this fusion protein in tumorigenesis in vivo has not been shown. We determined whether expression of Pax3-FKHR in the mouse germ line would render these animals prone to the development of rhabdomyosarcomas. By targeting FKHR cDNA sequences into the Pax3 locus of embryonic stem cells, we used these cells to generate mice carrying a Pax3-FKHR knock-in allele. Despite low expression of the knock-in allele, heterozygous offspring of Pax3-FKHR chimeric mice showed developmental abnormalities. These included intraventricular septum defects, tricuspid valve insufficiency, and diaphragm defects, which caused congestive heart failure leading to perinatal death. In addition, Pax3-FKHR heterozygous offspring displayed malformations of some but not all hypaxial muscles. However, neither newborn heterozygous pups nor their chimeric parents showed any signs of malignancy. We conclude that the Pax3-FKHR allele causes lethal developmental defects in knock-in mice but might be insufficient to cause muscle tumors.


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