Mechanism of resistance of yoshida sarcoma to nitrogen mustard

Inaba, Makoto; Sakurai, Yoshio

doi:10.1002/ijc.2910070308

Cited by 11 publications

(3 citation statements)

References 9 publications

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“…Further evidence was added for suppressed transport through the cell membranes of the resistant lines. Damage to cell membranes was proved by vital staining when a concentration of SH-blocking agents in the pretreatment reached a certain level, and the binding rate of H N , to D N A of the resistant lines was recovered almost to the same level of the sensitive line by this pretreatment.However, the binding rate of the sensitive line was not changed by pretreatment with the blocking agents at any concentrations.The following results were reported in our previous paper on the mechanism of acquired resistance of Yoshida sarcoma to nitrogen mustard (Inaba and Sakurai, 1971). …”

supporting

confidence: 56%

“…The following results were reported in our previous paper on the mechanism of acquired resistance of Yoshida sarcoma to nitrogen mustard (Inaba and Sakurai, 1971).…”

supporting

confidence: 54%

“…Fractionation of cellular components such as RNA, DNA, and protein was carried out by a modified method of Ogur and Rosen. The methods used in these experiments were described in detail in the previous report (Inaba and Sakurai, 1971).…”

Section: Uptake and Binding Of H N To The Cellular Constituentsmentioning

confidence: 99%

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Mechanism of resistance of Yoshida sarcoma to nitrogen mustard. II. Further evidence for suppressed transport of nitrogen mustard

Inaba

Moriwaki

Sakurai

1972

Intl Journal of Cancer

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Sensitivity of Yoshida sarcoma lines resistant to nitrogen mustard ( H N , ) was not enhanced by pretreatment in vitro with SH-blocking agents such as 2,2'-dithiodipyridine. This fact seems to indicate that content of cellular sulfhydryl groups did not play a great role in acquisition of resistance to HN,. No difference was observed between the sensitive and resistant lines in retention rate of H N , bound to D N A of the cells during incubation of the cells in an HN,-free medium. These results suggested no considerable difference in the ability to repair D N A in both lines. Further evidence was added for suppressed transport through the cell membranes of the resistant lines. Damage to cell membranes was proved by vital staining when a concentration of SH-blocking agents in the pretreatment reached a certain level, and the binding rate of H N , to D N A of the resistant lines was recovered almost to the same level of the sensitive line by this pretreatment.However, the binding rate of the sensitive line was not changed by pretreatment with the blocking agents at any concentrations.The following results were reported in our previous paper on the mechanism of acquired resistance of Yoshida sarcoma to nitrogen mustard (Inaba and Sakurai, 1971).(1) There was a proportional relationship between the rate of binding of nitrogen mustard (HN,) with the cellular constituents such as DNA and the resistance index when the cells were incubated in vitro in a medium containing HN,. The higher the resistance index, the lower was the binding rate.(2) The uptake of HN, by the cells through the membrane was found to be greater in the sensitive line than in the resistant lines, but the rate of uptake was not proportional to the resistance index, two resistant lines having indices of 100 and 1,000, respectively, showing a similar rate of uptake.From these results it appeared that a decrease in membrane transport of resistant lines did not totally reflect the decrease in the rate of binding of HN, to DNA. The results suggested the possibility of another mechanism of resistance; for example, enhancement of HN,-inactivating capacity and DNA-repairing activity of the cells of resistant lines. The present paper deals with further experiments on the suppressed membrane transport of the resistant cells, and inactivation of HN, by the cellular sulfhydryl groups. A brief survey on the loss of SH-HNz bound to DNA of sensitive and resistant cells is also reported. MATERIAL AND METHODS Resistant sublines of Yoshida sarcomaYSc-,(, and YSc-,4, having resistance indices of 2,500, were used as resitant sublines. These cell lines were obtained by successive contact of YSc-,, used in the previous work with HN,. Chemical Company (Osaka, Japan) and Tokyo Chemical Industry Co., Ltd. (Tokyo, Japan), respectively. 6,6'-Dithiodinicotinic acid (CPDS) was synthesized in our laboratory following the method reported by Fox and Gibas (1958) and identified by melting point, infra-red, and ultraviolet spectra. 3H-Labelled nitrogen mustard (HN,) was prepared by ...

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supporting

confidence: 56%

“…The following results were reported in our previous paper on the mechanism of acquired resistance of Yoshida sarcoma to nitrogen mustard (Inaba and Sakurai, 1971).…”

supporting

confidence: 54%

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Mechanism of resistance of Yoshida sarcoma to nitrogen mustard. II. Further evidence for suppressed transport of nitrogen mustard

Inaba

Moriwaki

Sakurai

1972

Intl Journal of Cancer

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Mechanism of resistance of yoshida sarcoma to nitrogen mustard. III. Mechanism of supressed transport of nitrogen mustard

Inaba

1973

Intl Journal of Cancer

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Mechanism of decreased transport of nitrogen mustard ( H N , ) in HN,-resistant Yorhida sarcoma cells was investigated. H N , uptake byFrom our previous data (Inaba e f al., 1971(Inaba e f al., , 1972 it became evident that membrane transport of HN, was suppressed by HN,-resistant Yoshida sarcoma. This was demonstrated by the lowered gross HN, uptake by some resistant sublines and also by a parallel increase in the binding rate of HN, to DNA with damage of cellular membrane of resistant cells.It was of interest to ascertain the relationship between drug binding to DNA and membrane transport, since the inhibition in rate of HN, uptake in some resistant sublines was not as large as the inhibition of its binding to cellular components. This phenomenon could be explained by the presence of other mechanisms which inhibit the binding of HN2 or by the difficulty of obtaining accurate quantitative measurement of HN2 transport. The latter point was discussed by Wolpert and Ruddon (L969) in detail.Another point of interest is the mechanism responsible for depression of HN, transport in the resistant cells. The work described in this paper was designed to shed light on these problems. MATERIAL A N D METHODS Resistant sublines of Yoshida sarcomaSublines RA,-,,, RAc-22, RAc-28: These three sublines acquired 5,000-, 10,000-, and 10,000-fold resistance, respectively, several years ago by repeated contact with HN, in vitro. At present, they show the same resistance index of 100.Sublines YS

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Mechanism of Action of 2-Chloroethylamine Derivatives, Sulfur Mustards, Epoxides, and Aziridines

Connors¹

1975

Antineoplastic and Immunosuppressive Agents

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Mechanism of resistance of yoshida sarcoma to nitrogen mustard

Abstract: Uptake and binding of methyl-his (2-chloroethy1)amine hydrochloride (HN,)

Cited by 11 publications

References 9 publications

Mechanism of resistance of Yoshida sarcoma to nitrogen mustard. II. Further evidence for suppressed transport of nitrogen mustard

Mechanism of resistance of Yoshida sarcoma to nitrogen mustard. II. Further evidence for suppressed transport of nitrogen mustard

Mechanism of resistance of yoshida sarcoma to nitrogen mustard. III. Mechanism of supressed transport of nitrogen mustard

Mechanism of Action of 2-Chloroethylamine Derivatives, Sulfur Mustards, Epoxides, and Aziridines

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