The sensitivity of a yoshida sarcoma to methylene dimethane sulphonate

Fox, Brian W

doi:10.1002/ijc.2910040108

Cited by 34 publications

(12 citation statements)

References 17 publications

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“…Small pieces of tumour tissue (approximately 5 mm 3) were transplanted subcutaneously by trochar implantation into the flank of the animal. The tumour volume was measured as previously described (Fox, 1969) (Gregory and Lajtha, 1970 (Fig. 1).…”

Section: Methodsmentioning

confidence: 99%

“…MDMS given to rats prior to tumour transplantation also acted as an immunosuppressant in this system resulting in an increased rate of tumour growth. For both responses the maximum immunosuppressive effect was obtained when the interval between drug administration and antigenic challenge was minimal.METHYLENE dimethane sulphonate (MDMS) has been shown (Fox and Jackson, 1965;Fox, 1969) to exert an excellent anti-tumour action on the transplanted Yoshida lymphosarcoma in the Wistar rat. This tumour is equivalent to an allograft system, but the host reaction against the transplantation antigens, although great, does not normally reject the tumour which eventually kills the animal.…”

mentioning

confidence: 99%

“…METHYLENE dimethane sulphonate (MDMS) has been shown (Fox and Jackson, 1965;Fox, 1969) to exert an excellent anti-tumour action on the transplanted Yoshida lymphosarcoma in the Wistar rat. This tumour is equivalent to an allograft system, but the host reaction against the transplantation antigens, although great, does not normally reject the tumour which eventually kills the animal.…”

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confidence: 99%

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A Study of the Immunosuppressive Activity of Methylene Dimethane Sulphonate (MDMS) in Relation to its Effectiveness as an Anti-Tumour Agent

Fox¹,

Gregory²

1972

Br J Cancer

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Summary.-The anti-tumour action of methylene dimethane sulphonate (MDMS) has been further investigated in relation to its immunosuppressive properties. Following a dose of 10 mg/kg, the proportion of permanent regressions of Yoshida lymphosarcoma transplants is lower in animals treated during the first 5 days of tumour growth. Re-implants on day 28 to those animals in which regression of the tumour had occurred indicated that the immune response to the tumour increases during the first 7 days of tumour growth.Studies of the effect of MDMS on the primary antibody-forming cell response of mice to sheep red cell antigens showed this drug to be an immunosuppressant comparable in strength to x-radiation. MDMS given to rats prior to tumour transplantation also acted as an immunosuppressant in this system resulting in an increased rate of tumour growth. For both responses the maximum immunosuppressive effect was obtained when the interval between drug administration and antigenic challenge was minimal.METHYLENE dimethane sulphonate (MDMS) has been shown (Fox and Jackson, 1965;Fox, 1969) to exert an excellent anti-tumour action on the transplanted Yoshida lymphosarcoma in the Wistar rat. This tumour is equivalent to an allograft system, but the host reaction against the transplantation antigens, although great, does not normally reject the tumour which eventually kills the animal. Although tumour-specific antigens probably play a minor role in determining the host reaction against it, this system does provide a useful model system to study the contribution of host immunity to the chemotherapeutic effect of an anti-tumour drug (Mihich, 1969). The factors influencing drug-induced remission have been reviewed by Goldin (1969) and Mandel and Rall (1969).The results of the present study indicate that the effectiveness of MDMS as an anti-tumour agent varies according to the level of immunity developed in the tumour-bearing host. We have also found that MDMS like other members of this series of bifunctional alkylating agents (Berenbaum, Timmis and Brown, 1967) possesses immunosuppressive properties as well as tumour cytotoxicity and the net effect of these two opposing activities in terms of tumour regression, depends on the time of MDMS administration relative to the time of tumour transplantation. MATERIALS AND METHODSMethylene dimethane sulphonate was prepared as previously described (Fox and Jackson, 1965) and injected intraperitoneally in physiological saline (2-5 mg/ml). All solutions were prepared under chilled conditions immediately before use to avoid breakdown of the drug due to hydrolysis.For the tumour growth studies, female Wistar rats (150-200 g, 8 to 10 weeks old) * Present address:

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Section: Methodsmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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A Study of the Immunosuppressive Activity of Methylene Dimethane Sulphonate (MDMS) in Relation to its Effectiveness as an Anti-Tumour Agent

Fox¹,

Gregory²

1972

Br J Cancer

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“…Thus, at the time of the second treatment a much higher number of cells survive and they, in addition to the resistance developed by absorption of the factor, may develop their own resistance due to further selection. In this way, resistance of the majority of the cell population could develop after a single treatment, as is observed in some instances after in vivo exposure of the Yoshida sarcoma to MDMS (Fox, 1969).…”

Section: C"o-culture Of Sensitive and Resistant Cellsmentioning

confidence: 88%

“…The MDMS-sensitive (YS) and MDMSresistant (YR) Yoshida sarcoma cell lines were used, developed in vivo by Fox (1969) and isolated in vitro by Fox and Fox (1971). MDMS was prepared as described previously (Fox and Jackson, 1965).…”

Section: Materials Ani) Methodsmentioning

confidence: 99%

A Transferable “Resistance Factor” from in vitro Cultured MDMS-Resistant Yoshida Sarcoma Cells

Szende¹,

Fox²,

Fox³

1973

Br J Cancer

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Summary.-Cells of the methylene dimethanesulphonate -(MDMS) -resistant Yoshida sarcoma cell line contain a low molecular weight " resistance factor " which is present in the culture medium of these cells and may be utilized by MDMS-sensitive Yoshida sarcoma cells either by co-culturing the two cell lines or by culturing the MDMS-sensitive Yoshida cells in a medium containing 20% used medium of MDMSresistant Yoshida cells or in the presence of dialysed medium from resistant cells. The " resistance factor " does not inactivate the drug itself or its metabolites, and it has no influence on the sensitivity of the cells if added after MDMS treatment. Twenty-four hours seems to be enough time for the transfer of the resistance factor, but its effect on whole populations decreases within 24 hours of ceasing the supply. The relationship between these findings and the known phenomena of metabolic co-operation are discussed.

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Melphalan‐induced chromosome damage in sensitive and resistant human melanoma cell lines

Parsons

Morrison

1978

Intl Journal of Cancer

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Twelve consecutive treatments of a human melanoma cell line (MM253) with melphalan gave a subline (MM253-12M) which was five times more resistant to melphalan with respect to survival. In contrast to mustard-resistant rodent cells, the MM253-12M line had a higher stemline number than the parent line while growth rate and cell and colony morphology were unchanged. A further melphalan treatment following attempted mutagenesis with UV did not increase resistance. In a comparison of these two lines with two melanoma lines derived from other patients and the rat XC line, resistance was correlated with lower frequency of melphalan-induced chromosome aberrations, determined 48 h after a 4-h exposure to melphalan (3 microgram/ml). In the two cell lines studied, aberration-free metaphase cells from treated culture had fewer chromosomes than untreated cells. DNA synthesis studied in the 4- to 72-h period after treatment was inhibited to the same extent in MM253 and MM253-12M cells at 4 microgram/ml but to a greater extent in the sensitive line at 0.1-1.5 microgram/ml. During the first hour of treatment at 0.1-1.5 microgram/ml, DNA synthesis in MM253 appeared to be enhanced.

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The sensitivity of a yoshida sarcoma to methylene dimethane sulphonate

Cited by 34 publications

References 17 publications

A Study of the Immunosuppressive Activity of Methylene Dimethane Sulphonate (MDMS) in Relation to its Effectiveness as an Anti-Tumour Agent

A Study of the Immunosuppressive Activity of Methylene Dimethane Sulphonate (MDMS) in Relation to its Effectiveness as an Anti-Tumour Agent

A Transferable “Resistance Factor” from in vitro Cultured MDMS-Resistant Yoshida Sarcoma Cells

Melphalan‐induced chromosome damage in sensitive and resistant human melanoma cell lines

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