N-Bromoacetyl-β-D-glucosamine tetra-O-acetate and N-bromoacetyl-β-D-galactosamine tetra-O-acetate as chemotherapeutic agents with immunopotentiating effects in Ehrlich ascites tumor-bearing mice

P. Simon, W. J. Burlingham, R. Conklin, Thomas P Fondy

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Abstract

N-Bromoacetyl-β-D-glucosamine tetra-O-acetate (NBrAcGlc-TA) and N-bromoacetyl-β-D-galactosamine tetra-O-acetate (NBrAcGal-TA) produced strong in vitro cytotoxicity against both Ehrlich and L1210 leukemia dividing cell lines at μM concentrations. A single administration i.p. at one-half the dose lethal to 10% of the animals of either agent cured 85% of Ehrlich ascites tumor-bearing C57BL/6J x DBA/2 (hereafter called B6D2F1) mice. Animals immunosuppressed by prior X-irradiation could not be cured by these agents. The corresponding chloro and fluoroderivatives and the non-O-acetylated N-haloacetylhexosamines were inactive in vitro and in vivo. No significant effect against L1210 leukemia in vivo was obtained with any of these agents. Cure of immunocompetent mice was associated with strong but incomplete cytotoxicity within 24 hr following drug administration and with a simultaneous increase in peritoneal polymorphonuclear leukocytes. Immunosuppressed mice also showed marked cytotoxic reduction in Ehrlich cell number, but the animals died from resumed tumor growth. Immunocompetent tumor-bearing mice after drug treatment exhibited complete resistance to an additional, normally lethal, challenge with 106 Ehrlich cells within 24 hr after drug treatment and from 1 to 9 weeks after drug-induced cure were completely resistant to 107 Ehrlich cells. Mice treated i.p. with NBrAcGlc-TA or NBrAcGal-TA 24 hr prior to implantation of 106 Ehrlich ascites cells exhibited increased survival time or in some cases complete resistance to this otherwise lethal challenge. NBrAcGal-TA was not immunosuppressive at the dose level that was used in chemotherapy when primary immunoglobulins M and G response to sheep erythrocytes was tested. Ehrlich cells killed in vitro by exposure to NBrAcGlc-TA or NBrAcGal-TA or to other antineoplastic alkylating agents and reimplanted in vivo at a level comparable to that used in the in vivo cured mice failed to generate resistance to rechallenge with viable Ehrlich cells. It appears that NBrAcGlc-TA and NBrAcGal-TA exert anti-Ehrlich tumor activity in vivo by functioning as lipophilic alkylating agents that are cytotoxic to the tumor cells while concurrently enhancing the host response to the tumor.

Original languageEnglish (US)
Pages (from-to)3897-3902
Number of pages6
JournalCancer Research
Volume39
Issue number10
StatePublished - 1979

Fingerprint

Ehrlich Tumor Carcinoma
Galactosamine
Acetates
Leukemia L1210
Neoplasms
Pharmaceutical Preparations
Alkylating Antineoplastic Agents
N-bromoacetylglucosamine
Alkylating Agents
Immunosuppressive Agents
Ascites
Immunoglobulin M
Sheep
Neutrophils
Cell Count
Immunoglobulin G
Erythrocytes
Drug Therapy
Cell Line

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

@article{b02bd4b83a52415f8e391d4a5556b2c8,
title = "N-Bromoacetyl-β-D-glucosamine tetra-O-acetate and N-bromoacetyl-β-D-galactosamine tetra-O-acetate as chemotherapeutic agents with immunopotentiating effects in Ehrlich ascites tumor-bearing mice",
abstract = "N-Bromoacetyl-β-D-glucosamine tetra-O-acetate (NBrAcGlc-TA) and N-bromoacetyl-β-D-galactosamine tetra-O-acetate (NBrAcGal-TA) produced strong in vitro cytotoxicity against both Ehrlich and L1210 leukemia dividing cell lines at μM concentrations. A single administration i.p. at one-half the dose lethal to 10{\%} of the animals of either agent cured 85{\%} of Ehrlich ascites tumor-bearing C57BL/6J x DBA/2 (hereafter called B6D2F1) mice. Animals immunosuppressed by prior X-irradiation could not be cured by these agents. The corresponding chloro and fluoroderivatives and the non-O-acetylated N-haloacetylhexosamines were inactive in vitro and in vivo. No significant effect against L1210 leukemia in vivo was obtained with any of these agents. Cure of immunocompetent mice was associated with strong but incomplete cytotoxicity within 24 hr following drug administration and with a simultaneous increase in peritoneal polymorphonuclear leukocytes. Immunosuppressed mice also showed marked cytotoxic reduction in Ehrlich cell number, but the animals died from resumed tumor growth. Immunocompetent tumor-bearing mice after drug treatment exhibited complete resistance to an additional, normally lethal, challenge with 106 Ehrlich cells within 24 hr after drug treatment and from 1 to 9 weeks after drug-induced cure were completely resistant to 107 Ehrlich cells. Mice treated i.p. with NBrAcGlc-TA or NBrAcGal-TA 24 hr prior to implantation of 106 Ehrlich ascites cells exhibited increased survival time or in some cases complete resistance to this otherwise lethal challenge. NBrAcGal-TA was not immunosuppressive at the dose level that was used in chemotherapy when primary immunoglobulins M and G response to sheep erythrocytes was tested. Ehrlich cells killed in vitro by exposure to NBrAcGlc-TA or NBrAcGal-TA or to other antineoplastic alkylating agents and reimplanted in vivo at a level comparable to that used in the in vivo cured mice failed to generate resistance to rechallenge with viable Ehrlich cells. It appears that NBrAcGlc-TA and NBrAcGal-TA exert anti-Ehrlich tumor activity in vivo by functioning as lipophilic alkylating agents that are cytotoxic to the tumor cells while concurrently enhancing the host response to the tumor.",
author = "P. Simon and Burlingham, {W. J.} and R. Conklin and Fondy, {Thomas P}",
year = "1979",
language = "English (US)",
volume = "39",
pages = "3897--3902",
journal = "Journal of Cancer Research",
issn = "0008-5472",
publisher = "American Association for Cancer Research Inc.",
number = "10",

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TY - JOUR

T1 - N-Bromoacetyl-β-D-glucosamine tetra-O-acetate and N-bromoacetyl-β-D-galactosamine tetra-O-acetate as chemotherapeutic agents with immunopotentiating effects in Ehrlich ascites tumor-bearing mice

AU - Simon, P.

AU - Burlingham, W. J.

AU - Conklin, R.

AU - Fondy, Thomas P

PY - 1979

Y1 - 1979

N2 - N-Bromoacetyl-β-D-glucosamine tetra-O-acetate (NBrAcGlc-TA) and N-bromoacetyl-β-D-galactosamine tetra-O-acetate (NBrAcGal-TA) produced strong in vitro cytotoxicity against both Ehrlich and L1210 leukemia dividing cell lines at μM concentrations. A single administration i.p. at one-half the dose lethal to 10% of the animals of either agent cured 85% of Ehrlich ascites tumor-bearing C57BL/6J x DBA/2 (hereafter called B6D2F1) mice. Animals immunosuppressed by prior X-irradiation could not be cured by these agents. The corresponding chloro and fluoroderivatives and the non-O-acetylated N-haloacetylhexosamines were inactive in vitro and in vivo. No significant effect against L1210 leukemia in vivo was obtained with any of these agents. Cure of immunocompetent mice was associated with strong but incomplete cytotoxicity within 24 hr following drug administration and with a simultaneous increase in peritoneal polymorphonuclear leukocytes. Immunosuppressed mice also showed marked cytotoxic reduction in Ehrlich cell number, but the animals died from resumed tumor growth. Immunocompetent tumor-bearing mice after drug treatment exhibited complete resistance to an additional, normally lethal, challenge with 106 Ehrlich cells within 24 hr after drug treatment and from 1 to 9 weeks after drug-induced cure were completely resistant to 107 Ehrlich cells. Mice treated i.p. with NBrAcGlc-TA or NBrAcGal-TA 24 hr prior to implantation of 106 Ehrlich ascites cells exhibited increased survival time or in some cases complete resistance to this otherwise lethal challenge. NBrAcGal-TA was not immunosuppressive at the dose level that was used in chemotherapy when primary immunoglobulins M and G response to sheep erythrocytes was tested. Ehrlich cells killed in vitro by exposure to NBrAcGlc-TA or NBrAcGal-TA or to other antineoplastic alkylating agents and reimplanted in vivo at a level comparable to that used in the in vivo cured mice failed to generate resistance to rechallenge with viable Ehrlich cells. It appears that NBrAcGlc-TA and NBrAcGal-TA exert anti-Ehrlich tumor activity in vivo by functioning as lipophilic alkylating agents that are cytotoxic to the tumor cells while concurrently enhancing the host response to the tumor.

AB - N-Bromoacetyl-β-D-glucosamine tetra-O-acetate (NBrAcGlc-TA) and N-bromoacetyl-β-D-galactosamine tetra-O-acetate (NBrAcGal-TA) produced strong in vitro cytotoxicity against both Ehrlich and L1210 leukemia dividing cell lines at μM concentrations. A single administration i.p. at one-half the dose lethal to 10% of the animals of either agent cured 85% of Ehrlich ascites tumor-bearing C57BL/6J x DBA/2 (hereafter called B6D2F1) mice. Animals immunosuppressed by prior X-irradiation could not be cured by these agents. The corresponding chloro and fluoroderivatives and the non-O-acetylated N-haloacetylhexosamines were inactive in vitro and in vivo. No significant effect against L1210 leukemia in vivo was obtained with any of these agents. Cure of immunocompetent mice was associated with strong but incomplete cytotoxicity within 24 hr following drug administration and with a simultaneous increase in peritoneal polymorphonuclear leukocytes. Immunosuppressed mice also showed marked cytotoxic reduction in Ehrlich cell number, but the animals died from resumed tumor growth. Immunocompetent tumor-bearing mice after drug treatment exhibited complete resistance to an additional, normally lethal, challenge with 106 Ehrlich cells within 24 hr after drug treatment and from 1 to 9 weeks after drug-induced cure were completely resistant to 107 Ehrlich cells. Mice treated i.p. with NBrAcGlc-TA or NBrAcGal-TA 24 hr prior to implantation of 106 Ehrlich ascites cells exhibited increased survival time or in some cases complete resistance to this otherwise lethal challenge. NBrAcGal-TA was not immunosuppressive at the dose level that was used in chemotherapy when primary immunoglobulins M and G response to sheep erythrocytes was tested. Ehrlich cells killed in vitro by exposure to NBrAcGlc-TA or NBrAcGal-TA or to other antineoplastic alkylating agents and reimplanted in vivo at a level comparable to that used in the in vivo cured mice failed to generate resistance to rechallenge with viable Ehrlich cells. It appears that NBrAcGlc-TA and NBrAcGal-TA exert anti-Ehrlich tumor activity in vivo by functioning as lipophilic alkylating agents that are cytotoxic to the tumor cells while concurrently enhancing the host response to the tumor.

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