The Effect of Actinomycin on Regeneration Processes in Amphibians*†

Wolsky, Alexander; Doi, Nguyen Van

doi:10.1111/j.2164-0947.1965.tb02332.x

Cited by 5 publications

(2 citation statements)

References 22 publications

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“…Unlike VLB which causes metaphase arrest, Dactinomycin has little inhibitory effect on mitosis Wolsky, 1961, 1964). Yet the inhibi tion of regeneration is extensive, due to lack of differentiation (re generation blastema formation), and the inhibition o f regeneration follows a similar in both Atnbystoma and liana pipiens larvae (Wolsky and V a n Doi, 1965).…”

Section: Introductionmentioning

confidence: 99%

General and Selective Inhibition of Amphibian Regeneration by Vinblastine and Dactinomycin

Francoeur¹

1968

Oncology

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Section: Introductionmentioning

confidence: 99%

General and Selective Inhibition of Amphibian Regeneration by Vinblastine and Dactinomycin

Francoeur¹

1968

Oncology

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“…Much recent information has accrued through the local and systemic application of various antimetabolites [see review in Schmidt, 1968], Of interest are the stud ies of Bieber and H itchings[I959], Burnet and Liversage[I964], who moni tored the effects of chloramphenicol on regenerating Triturus, Wolsky and Van Doi [1965] and Carlson [1967] who described the inhibitory effects of actinomycin D on anuran and urodelan regeneration. Recently we demon strated [Procaccini and Doyle, 1970b;Procaccini el a!., 1969] that exter nally-applied streptomycin retards and inhibits regenerative capacity in lar val Rana pipiens and R. clamitans and produces a specific teratologic re sponse.…”

Section: Introductionmentioning

confidence: 99%

The Inhibition of Limb Regeneration in Adult <i>Diemictylus viridescens </i>Treated with Streptomycin

Procaccini¹,

Doyle²

1972

Oncology

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Having previously stressed quantita tive aspects of inhibition and the definition of the streptomycin induced response in anurans, the present study attempts a macroscopic and histologic analysis of inhibition of limb regeneration in the adult newt, D. viridescens, by streptomycin. This study confirmed earlier results that epidermal proliferation is not inhibited by the drug except in the highest concentrations; however, blastemal elements are markedly altered. It is thought that one of the important effects of streptomycin is its binding irreversibly to the ribosomal surface, and causing translational errors resulting in the production of inoperative proteins. The results suggest that the production of the blastemal mass and differentiation represent separate, partially synchronous, and coterminal processes. It may well be that the teratology seen in this experiment results not only from the production of missense or inoperative proteins by streptomycin but also from the unusual molecular ecology of the blastemal environment created by the abnormal dedifferentiation where fully dedifferentiated cells lie in close proximity to undifferentiated elements. Indirectly, this study has called attention to the unresolved problem of exactly which cells contribute to blastemal cell populations.

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Inhibition of limb regeneration in the axolotl after treatment of the skin with actinomycin D

Carlson¹

1969

Anat. Rec.

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In this experiment actinomycin D was used to explore the action of the wound epidermis on underlying tissues during limb regeneration. In axolotl forelimbs the skin was removed from the elbow to the shoulder. Skin from the right limbs was soaked for three hours in actinomycin D (5.0 or 10.0 ug/ml 0.6% NaC1). For controls, skin from left limbs was soaked in 0.6% NaCl for the same period of time. Each piece of skin was orthotopically replanted, and both limbs were amputated through the treated skin, proximal to the elbow. After an initial healing period, the control limbs regenerated normally. Except for a slightly paler color, limbs bearing actinomycin-treated skin were indistinguishable from the controls, both grossly and histologically, during the first week following amputation. While the control limbs formed early blastemas, no grossly visible evidence of regeneration was apparent in the experimental limbs, but histologically some dedifferentiation was occurring. Normally three to four digits were seen in the control regenerates before blastemas appeared on the experimental limbs. By 3 5 4 0 days blastemas had appeared on most experimental limbs. These developed very rapidly, and within a short time many of them had attained levels of development close to the controls. Actinomycin D temporarily suppresses formation of the apical epidermal cap and the subsequent aggregation of dedifferentiated cells into a blastema. When the effect wears off, an apical cap forms and the dedifferentiated cells quickly organize into a blastema and begin to differentiate.The outgrowth of a developing vertebrate extremity, whether it be in an embryo (ZwiUing, '61) or a regenerating limb (Thornton, '65), appears to be the morphological expression of a continuous interaction between the epidermal covering and the underlying mesodermal components. Of particular importance is a thickening of the epidermis over the tip of the growing limb. In the regenerating urodele limb, Thornton ('54) has called this structure the apical epidermal cap, and it seems to play a vital role in the distal migration of dedifferentiated cells and their eventual accumulation into a blastema (Steen and Thornton, '63; Thornton and Steen, '62). The factors which bring about the apical epidermal thickening and the manner in which the epidermis influences the underlying tissues have continued to elude characterization. The present experiment is an outgrowth of some previous work on the effect of actinomycin D upon limb regeneration in newts (Carlson, '66, '67a; Wolsky and VanDoi, '65). In animals given systemic doses of actinomycin D, certain disturbances were noted in the pattern of epithelialization of the wound surface of an ANAT. REC., 163: 389-402. amputated limb. These disturbances consisted primarily of a tremendous overgrowth and disarray of the wound epithelium. Since in systemically treated animals the wound epidermis was underlain by considerable cellular debris, it was not possible to exclude the indirect effects of general toxicity, namely ...

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The Effect of Actinomycin on Regeneration Processes in Amphibians*†

Cited by 5 publications

References 22 publications

General and Selective Inhibition of Amphibian Regeneration by Vinblastine and Dactinomycin

General and Selective Inhibition of Amphibian Regeneration by Vinblastine and Dactinomycin

The Inhibition of Limb Regeneration in Adult <i>Diemictylus viridescens </i>Treated with Streptomycin

Inhibition of limb regeneration in the axolotl after treatment of the skin with actinomycin D

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