Production of spinal curvatures in rats by chemically dissimilar substances

Dasler, Waldemar; Stoner, Ramon E.

doi:10.1007/bf02166706

Cited by 17 publications

(5 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our data do permit some comments concerning the specificity of BAPN binding. Dasler and Stoner (1959) have proposed that lathyrogens may serve as metal chelators, and evidence has been presented suggesting that the administration of copper partially reverses the effect of lathyrogens on connective tissue (Shields and Duffy, 1965). Administration of the copper chelator penicillamine inhibits covalent cross-link formation in elastin and collagen (Miller et al, 1965;Nimni, 1965).…”

Section: Discussionmentioning

confidence: 99%

Molecular Diseases of Connective and Vascular Tissues. II. Amine Oxidase Inhibition by the Lathyrogen, β-Aminopropionitrile^*

Page¹,

Benditt²

1967

Biochemistry

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

Molecular Diseases of Connective and Vascular Tissues. II. Amine Oxidase Inhibition by the Lathyrogen, β-Aminopropionitrile^*

Page¹,

Benditt²

1967

Biochemistry

View full text Add to dashboard Cite

“…Do Lathyrogens Act by Chdate FormationS--It has been proposed that lathyrogens may act as chelating agents (14); the results of testing chelate-forming agents such as versene and alizarin for lathyrogenlc activity did not support this proposition.…”

Section: Table V Effect Of Modifying --Nh~ Ending On Lathyrogenlx Aaivity Oj Semicarbazidementioning

confidence: 99%

“…Attempts to seek common chemical denominators among known lathyrogens (8,9), have met with little success with the exception of one study (10) in which it was shown that the lathyrogenic capacity of an organic nitrile is influenced by the presence of a reactive amino group. Yet another approach has been the search for a common functional denominator, such as that of monamine oxidase inhibition (11)(12)(13) or chelate formation (14), but these hypotheses remain unproven.…”

mentioning

confidence: 99%

Structural Requirements for Lathyrogenic Agents

Levene

1961

The Journal of Experimental Medicine

View full text Add to dashboard Cite

Collagen protein is generally regarded as having a small turnover in the adult; in certain situations however, such as the return to normal of the postpartum uterus of the rat (1) or the remodelling of a badly aligned healing fracture of long bone, collagen fibrils are resorbed, but the mechanisms involved remain elusive. Since one of the effects of lathyrogenic agents is thought to be a loosening of intermolecular collagen bonding (2, 3), lathyrism provides a potentially useful means with which to study the process of the disorgaz3ization of the collagen fibril. One such study on the metabolism of C14-nitrile-labelled aminoacetonitrile in the weanling rat (4) showed a wide distribution of the labelled carbon, the major part of which however remained unidentified. A later study of the metabolism of labelled fl-aminopropionitrile (BAPN) led to the identification of the major metabolic product, cyanoacetic acid, itself non-lathyrogenic, but the nature of the active molecule and its site of action remain unknown (5-7). Attempts to seek common chemical denominators among known lathyrogens (8, 9), have met with little success with the exception of one study (10) in which it was shown that the lathyrogenic capacity of an organic nitrile is influenced by the presence of a reactive amino group. Yet another approach has been the search for a common functional denominator, such as that of monamine oxidase inhibition (11-13) or chelate formation (14), but these hypotheses remain unproven.The major obstacle to these latter approaches has been the lack of clearly defined criteria of lathyrogenic activity, resulting in the inclusion of compounds of dubious activity; the criteria of activity in the rat, the usual assay animal, have been weight loss, skeletal deformity, neurological manifestations, and angiorrhexis. A rigid adherence to these criteria however, is misleading in such cases as the mature guinea pig where the administration of BAPN results not in skeletal deformity and angiorrhexis but solely in increased amounts of collagen extractable from the skin (15). Another assay system which relies on

show abstract

“…Dasler et aZ ( 1,2) have postulated that diverse chemical substances inducing spinal curvatures and other lathyritic symptoms in experimental animals may exert their effects by means of formation of coordination complexes or chelates. Mager et aZ (3) have reported that low levels of copper ions are necessary for the toxic action of aminoacetonitrile on fibroblasts in vitro.…”

mentioning

confidence: 99%

Effect of Lathyrogenic Aminonitriles, Related Amines, and Copper-Complexing Agents on Conidial Germination of Molds.

Norton

Dasler

1964

Experimental Biology and Medicine

Self Cite

View full text Add to dashboard Cite

Dasler et aZ( 1,2) have postulated that diverse chemical substances inducing spinal curvatures and other lathyritic symptoms in experimental animals may exert their effects by means of formation of coordination complexes or chelates. Mager et aZ(3) have reported that low levels of copper ions are necessary for the toxic action of aminoacetonitrile on fibroblasts in vitro. The well-known medial lesions in aortas of lathyritic animals bear a marked resemblance to those produced by copper deficiency in chicks(4) or pigs (5).Common molds are reported to be affected by trace elements and ion-complexing agents. Aspergillus niger requires Cu+ + for sporulation (6). The germinations of Neurospora tetrasperma conidia and activated ascospores are inhibited by ethylenediaminetetracetic acid (0.01 M ) , and at least partial reversal of these inhibitions can be obtained with Cu+ + ( 7 ) . We have found conidial germination of A . niger to be inhibited by Betaaminopropionitrile (BAPN) (8). Therefore, a comparison of the effect of aminonitriles and Cu++-complexing agents on spore germination was undertaken using A . niger and N . crassa, a species closely related to N . t etrasperma.Materials. A . niger (strain AN-6275) and N . crassa (strains NC-11943, histidine requiring; NC-10334, proline requiring; NC-9279, wild type) were obtained from American Type Culture Collection. BAPN acid fumarate (BAPN Fu) was obtained from Abbott Laboratories; BAPN free base from Calbiochem ; propioni trile, e thylenediamine dihydrochloride and ethylamine hydrochloride from Distillation Products, Inc. (Eastman) ; Dglucosamine hydrochloride, L-histidine monohydrochloride, and L-proline from Nutritional Biochemicals Corp. ; imidazole from General Biochemicals ; a,d-dipyridyl, 8-hy-* This study was supported by research grants from Nat. Inst. of Arthritis and Metab. D'is., U.S.P.H.S. droxyquinoline, reagent grade inorganic salts, and sucrose from Fisher Scientific Co. Aminoacetonitrile hydrochloride (AAN) was synthesized in our laboratory.Methods. Molds were grown on Neurospora culture agar (Difco 0321-15) used at 2/3 strength. I t was supplemented with 0.005 M histidine or 0.02 M proline when growing NC-11943 or NC-10334, respectively. Deionized water, made by passing distilled water thru a Crystalab water demineralizer, was used for preparation of all solutions.A . niger spores were obtained from an agar slant culture grown at 26"Ct for 2 9 to 3 days. They were harvested by suspension in potassium phosphate buffer a t concentrations ranging from 0.025 M to 0.1 M. The spore suspensions were dispersed by means of a Vortex Jr. mixer and diluted with buffer to an optical density of 0.5 at 560 mp (Coleman Universal Spectrophotometer) . After a further 1 : 20 dilution with spore germination media, the suspensions were inoculated onto slides (0.1 ml of suspension per slide). The slides and cover slips had been previously washed with detergent, soaked in 0.6 N HC1 for a t least a day, and rinsed 4 times with deionized water. N . crassa spores were treated...

show abstract

Production of spinal curvatures in rats by chemically dissimilar substances

Cited by 17 publications

References 5 publications

Molecular Diseases of Connective and Vascular Tissues. II. Amine Oxidase Inhibition by the Lathyrogen, β-Aminopropionitrile^*

Molecular Diseases of Connective and Vascular Tissues. II. Amine Oxidase Inhibition by the Lathyrogen, β-Aminopropionitrile^*

Structural Requirements for Lathyrogenic Agents

Effect of Lathyrogenic Aminonitriles, Related Amines, and Copper-Complexing Agents on Conidial Germination of Molds.

Contact Info

Product

Resources

About

Production of spinal curvatures in rats by chemically dissimilar substances

Cited by 17 publications

References 5 publications

Molecular Diseases of Connective and Vascular Tissues. II. Amine Oxidase Inhibition by the Lathyrogen, β-Aminopropionitrile*

Molecular Diseases of Connective and Vascular Tissues. II. Amine Oxidase Inhibition by the Lathyrogen, β-Aminopropionitrile*

Structural Requirements for Lathyrogenic Agents

Effect of Lathyrogenic Aminonitriles, Related Amines, and Copper-Complexing Agents on Conidial Germination of Molds.

Contact Info

Product

Resources

About

Molecular Diseases of Connective and Vascular Tissues. II. Amine Oxidase Inhibition by the Lathyrogen, β-Aminopropionitrile^*

Molecular Diseases of Connective and Vascular Tissues. II. Amine Oxidase Inhibition by the Lathyrogen, β-Aminopropionitrile^*