Liarozole Markedly Increases all trans-Retinoic Acid Toxicity in Mouse Limb Bud Cell Cultures: A Model to Explain the Potency of the Aromatic Retinoid (E)-4-[2-(5,6,7,8-Tetrahydro-5,5,8,8-tetramethyl-2-naphthylenyl)-1-propenyl] Benzoic Acid

2002 ◽  
Vol 178 (3) ◽  
pp. 186-194 ◽  
Author(s):  
Michael A Pignatello ◽  
Frederick C Kauffman ◽  
Arthur A Levin
Keyword(s):  
Retinoic Acid ◽  
Benzoic Acid ◽  
Cell Cultures ◽  
Limb Bud ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Mouse Limb ◽  
Acid Toxicity ◽  
Aromatic Retinoid

scholarly journals The epithelial differentiating activity in vivo of (E)-4-[2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthylenyl) −1-propenyl]benzoic acid and 4,4-difluororetinoic acid

1985 ◽  
Vol 227 (1) ◽  
pp. 311-316 ◽  
Author(s):  
D A Miller ◽  
A Stephens-Jarnagin ◽  
H F DeLuca
Keyword(s):  
Retinoic Acid ◽  
Benzoic Acid ◽  
Female Rats ◽  
Vaginal Smear ◽  
Deficient Diet ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Housing Facilities ◽  
Made In

Female rats fed on a vitamin A-deficient diet from weaning were oophorectomized after introitus and used to test analogues of all-trans-retinoic acid for epithelial differentiation activity by the vaginal-smear assay. Several modifications have been made in the assay; housing facilities were modified, the diet changed and the existing scoring system for the assay altered. The arotinoid (E)-4-[2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthylenyl)-1 -propenyl] benzoic acid was 12-fold more active than all-trans-retinoic acid, which had a 50% effective dose (ED50) of 80 pmol/vagina. The fluorinated analogue 4,4-difluororetinoic acid had an ED50 of 2.5 nmol/vagina and was therefore 30-fold less active than all-trans-retinoic acid.

All-trans retinoic acid toxicity

2009 ◽  
Vol 49 (3) ◽  
pp. 148-149 ◽  
Author(s):  
K.G. Hem ◽  
G.J. Ossenkoppele
Keyword(s):  
Retinoic Acid ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Acid Toxicity

scholarly journals Studies on the mechanism of retinoid-induced pattern duplications in the early chick limb bud: temporal and spatial aspects.

1985 ◽  
Vol 101 (5) ◽  
pp. 1913-1920 ◽  
Author(s):  
G Eichele ◽  
C Tickle ◽  
B M Alberts
Keyword(s):  
Spatial Distribution ◽  
Retinoic Acid ◽  
Limb Bud ◽  
Lag Phase ◽  
Temporal And Spatial Distribution ◽  
Metabolic Pattern ◽  
Continuous Release ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Temporal And Spatial

All-trans-retinoic acid causes striking digit pattern changes when it is continuously released from a bead implanted in the anterior margin of an early chick wing bud. In addition to the normal set of digits (234), extra digits form in a mirror-symmetrical arrangement, creating digit patterns such as a 432234. These retinoic acid-induced pattern duplications closely mimic those found after grafts of polarizing region cells to the same positions with regard to dose-response, timing, and positional effects. To elucidate the mechanism by which retinoic acid induces these pattern duplications, we have studied the temporal and spatial distribution of all-trans-retinoic acid and its potent analogue TTNPB in these limb buds. We find that the induction process is biphasic: there is an 8-h lag phase followed by a 6-h duplication phase, during which additional digits are irreversibly specified in the sequence digit 2, digit 3, digit 4. On average, formation of each digit seems to require between 1 and 2 h. The tissue concentrations, metabolic pattern, and spatial distribution of all-trans-retinoic acid and TTNPB in the limb rapidly reach a steady state, in which the continuous release of the retinoid is balanced by loss from metabolism and blood circulation. Pulse-chase experiments reveal that the half-time of clearance from the bud is 20 min for all-trans-retinoic acid and 80 min for TTNPB. Manipulations that change the experimentally induced steep concentration gradient of TTNPB suggest that a graded distribution of retinoid concentrations across the limb is required during the duplication phase to induce changes in the digit pattern. The extensive similarities between results obtained with retinoids and with polarizing region grafts raise the possibility that retinoic acid serves as a natural "morphogen" in the limb.

scholarly journals Modifying Effects of 1'-Acetoxychavicol Acetate (ACA) and the Novel Synthetic Retinoids Re-80, Am-580 and Am-55P in a Two-Stage Carcinogenesis Model in Female Rats

2004 ◽  
Vol 32 (2) ◽  
pp. 250-257 ◽  
Author(s):  
Shinichiro Orita ◽  
Masao Hirose ◽  
Satoru Takahashi ◽  
Katsumi Imaida ◽  
Nobuyuki Ito ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Benzoic Acid ◽  
Female Rats ◽  
General Interest ◽  
High Dose ◽  
The Novel ◽  
Two Stage ◽  
Experimental Conditions ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid

Effects of dietary administration of 1'-acetoxychavicol acetate (ACA) and the novel synthetic retinoids 4-[1-hydroxy-3-oxo-3-(5,6,7,8-tetrahydro-3-hydroxy-5,5,8,8-tetramethyl-2-naphthalenyl)-1-propenyl]benzoic acid (Re-80); 4-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)carboxamido]benzoic acid (Am-580); and 6-[(3,5-di-tert-butylphenyl) carbamoyl]nicotinic acid (Am-55P) were examined using a two-stage rat carcinogenesis model. A total of 190 female SD rats was treated sequentially with 1,2-dimethylhydrazine (DMH, s.c.); 7,12-dimethylbenz(a)anthracene (DMBA, i.g.); and 2,2'-dihydroxy-di- n-propylnitrosamine (DHPN, in the drinking water) during the first three weeks (DDD-initiation), and an additional 60 rats received the vehicle alone (non-initiation). One week after the completion of the initiation period, they were divided into nine groups and administrated Re-80 (at dose levels of 1.0 or 0.4 ppm), Am-580 (20 or 4 ppm), Am-55P (20 ppm), ACA (100 ppm), all- trans-retinoic acid (10 or 2 ppm) or no supplement in the diet for 33 weeks, until survivors were euthanatized at week 37 weeks. After DDD-initiation, all- trans-retinoic acid at the high dose delayed the development of mammary tumors. The multiplicity of colon tumors in the group fed Am-55P and the incidences of nephroblastomas with ACA or Am-580 were decreased as compared with the control values, but the other chemicals had no modifying effects on tumor development in any organs. Thus, among ACA and the novel synthetic retinoids tested, only Am-55P showed a weak inhibitory effect on a neoplasm of general interest under the present experimental conditions.

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