Carbamates in the Chemotherapy of Leucemia

Bryan, Carl E.; Skipper, Howard E.; White, Locke

doi:10.1016/s0021-9258(18)57039-3

Cited by 33 publications

(2 citation statements)

References 8 publications

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“…or less per gin. mouse is excreted within 24 hours (24). Also it has been shown that lung tissue implanted 24 hours after injection of the hosts with urethane develops no growths though exposure of mice to urethane after implantation results in the occurrence of many tumors in the implanted tissue (25).…”

Section: Influence Of Dna Its Rate Of Synthesis Certain Of Its Constituents and Certain Of Tkeir Precursors Upon Tke Carcinogenic E:ffe~tmentioning

confidence: 99%

“…This is shown in representative accompanying charts (1 through 8). No test substance was given after injection of the animals with urethane because only the initiatory phase of carcinogenesis was to be studied (24,12,25). The experimental and control animals were similarly maintained after injection to insure that the subsequent growth of the neoplasms would take place under the same conditions.…”

Section: Findings In Experiments 1 Througk 30 (Tablementioning

confidence: 99%

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Studies of the Mechanism of Action of Urethane in Initiating Pulmonary Adenomas in Mice

Rogers

1957

The Journal of Experimental Medicine

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Urethane (ethyl carbamate) is a broad spectrum carcinogen which has been demonstrated to produce neoplasms of the lungs (1), liver (2), mesenchyreal tissue (3), and skin (4) in at least two species, the mouse and the rat. Because of the simplicity of its chemical structure it has proved a particularly interesting carcinogen for those studying the mechanism of carcinogenesis by classic chemical means. Studies of the carcinogenicity (5) or mitotic poisoning effects (6) of various esters of carbamic acid chemically related to urethane, the carcinogenicity of alkylated urethanes (7), of potential urethane degradation products (8), and a wide variety of general hypnotics (9) have, however, yielded no information upon the mechanism of action of urethane other than its relation to the specificity of the molecular structure of urethane. Observations on the influence of urethane on enzymatic and other less discrete in vitro systems have not yet been correlated with its carcinogenic or antileukemic action though they have given rise to many interesting speculations (10). Because the general biological importance of nucleic acid to the maintenance of heritable characteristics is generally recognized and, because of the nuclear poisoning effects of urethane (11), much attention has been directed toward the carcinogen's possible influence upon nucleic acid synthesis. Recent experiments have discounted the assumption that urethane has a direct nucleotoxic action in initiating tumors (5,6,12). Evidence perhaps in favor of an influence upon nucleic acids, however, has been reported by Cowen (13). Since the effect of pentosenucleotides on leucocytes is the opposite of that of urethane, he tested the protective effect of these substances upon its carcinogenic action. Fewer pulmonary tumors developed in mice receiving multiple injections of these nucleotides. However, the nucleotides were largely given after urethane injections had been discontinued. In addition, the tested animals suffered severe ill effects, thereby casting considerable doubt upon the validity of the results; for it is well known that the state of the animal influences greatly the overt occurrence and growth of tumors (14).

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Section: Influence Of Dna Its Rate Of Synthesis Certain Of Its Constituents and Certain Of Tkeir Precursors Upon Tke Carcinogenic E:ffe~tmentioning

confidence: 99%

Section: Findings In Experiments 1 Througk 30 (Tablementioning

confidence: 99%

Studies of the Mechanism of Action of Urethane in Initiating Pulmonary Adenomas in Mice

Rogers

1957

The Journal of Experimental Medicine

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Die Anwendung von radioaktiven und stabilen Isotopen in der pharmakologischen Forschung

Frimmer¹

1952

Angewandte Chemie

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den anderen Hefesterolen 27 C-Atome enthalt. Bei ihrn ist die Kondensation an C,, nicht eingetreten. Man kann dies so erklaren, dal3 in ihrn durch Wanderung der Doppeibindung C, -C, , in Konjugation zu der in C,,-C,,, die zur Kondensation an C,, notwendige CH,-Gruppe verschwand, so dal3 das Zymosterol im Gegensatz zu allen anderen Hefesterolen auf der C,,-Stufe verbleibt. Durch Hydrierung in 1 ,I-Stellung oder durch nachtragliche Verschiebung einer bei der biochemischen Hydrierung verbleibenden Doppelbindung nach C,,-C,, konnte so die Seitenkette des Zymosterols gebildet werden. Fur das tierische Cholesterol durfte entweder der Mangel an geeigneten C,-oder C,-Partnern in der Zelle oder eine Z U schnelle Absattigung der Doppelbindungen die Ursache sein, dal3 in ihm die Seitenkette nicht weiter substituiert wird. SchluRbemerkungDie letzten Jahrzehnte haben auf dem Steroidgebiet eine Fulle von neuen Erkenntnissen und Entdeckungen gebracht, und das Tatsachenmaterial wird sich, vermutlich vornehmlich aus dem Pflanzenreich, in den nachsten Jahren noch weiter vermehren. Es wird sich zeigen, wieweit die hier gezogenen Folgerungen eine Grundlage zur Klarung des biochemischen Syntheseweges der Sterole sein werden. Es wurde versucht, die bisherigen Ergebnisse unter dem ubergeordneten Gesichtspunkt dieser Synthese zu ordnen und so Anregungen zu geben, sich rnit diesem Gebiet durch weitere Versuche zu befassen. Dal3 es moglich war, schon so weitgehende Folgerungen zurn Syntheseweg der Steroide zu ziehen, wurde einmal durch das grol3e Tatsachemlaterial auf dem Gebiet der Cardenolide und Bufadienolide erreicht, das vor allem durch T . Reichstein in den letzten Jahren angesammelt worden ist, sowie bei den Spirostanolen durch R. E. Marker. Dann aber war es die gluckliche Auffindung des Mesogentiogenins und Picrotoxinins mit ihrer Konstitution, die sehr befruchtend auf die Bemuhungen zur Klarung des biochemischen Syntheseweges der Steroide wirken [A 465/456]

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Tissue‐specific induction of sister chromatid exchanges by ethyl carbamate in mice

Roberts

Allen

1980

Environ. mutagen

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Sister chromatid exchange (SCE) techniques were used to analyze the genetic effects of ethyl carbamate (urethane) in cultured mouse-bone marrow cells, and in several different mouse tissues in vivo. Ethyl carbamate concentrations up to 5.0 mg/ml were ineffective in causing a significant elevation of SCE in vitro. After in vivo drug administration, bone marrow, liver and spermatogonial cells all revealed significant dose-related increases in SCE. Baseline and relative incremental levels of SCE were somatic vs germ tissue-specific. Regenerating liver cells exhibited significantly greater absolute SCE values than all other tissues examined. Marrow cells revealed intermediate values, while germ cells were the least sensitive in SCE responsiveness. Spermatogonia required a fourfold higher dose, over that effective in somatic tissues, to promote an approximate doubling of the baseline SCE level. In vivo SCE analysis affords sensitive risk assessments for different tissues. Thus, this approach; should be generally useful for studying compounds with questionable mutagenic potential, and/or those exerting target organ specificities of related biological activity (eg, toxicity, carcinogenesis).

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Carbamates in the Chemotherapy of Leucemia

Cited by 33 publications

References 8 publications

Studies of the Mechanism of Action of Urethane in Initiating Pulmonary Adenomas in Mice

Studies of the Mechanism of Action of Urethane in Initiating Pulmonary Adenomas in Mice

Die Anwendung von radioaktiven und stabilen Isotopen in der pharmakologischen Forschung

Tissue‐specific induction of sister chromatid exchanges by ethyl carbamate in mice

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