Human tonsillar lymphocytes as targets for immunosuppressive and anticancer drugs

M. Staub, M. Sasvári, T. Spasokukotskaja, Zs Piróth, Z. Kazimierczuk

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

As has been shown earlier by us, the metabolism of extracellular deoxycytidine (dCyd) is 2-3 times higher in follicular and in PNA+ cells than in other cells. Deoxycytidine kinase (dCK) is one of the most important target enzymes for anti-proliferative drugs such as arabinoside-cytosine (ara-C), 2-Cl-deoxyadenosine (CdA). Neither the dCK activity nor the polypeptide correlates with the S phase of the cells, as thymidine kinase (TK1) does in tonsils. The newly developed anti-leukemic drug CdA, and also BrdA, are also phosphorylated by dCK and both effectively inhibit the 3H-dThd incorporation into DNA in tonsillar lymphocytes. A new molecular mechanism has been developed for CdA; it inhibits the interconversion of dCyd into dThd nucleotides. Analysis of the pools after 3H-dCyd labeling showed a decrease of the dUMP labeling. The inhibition of dCMP deaminase by the corresponding monophosphates (Cl-dAMP) in the cells has been suggested. CdA cannot be deaminated by adenosine deaminase (ADA), thus providing a good tool to investigate the importance of that enzyme during differentiation of the lymphoid cells. Elucidation of the nucleoside metabolism during the normal differentiation process might be the only way to get information about the same pathways in malignant transformations, i.e. in leukemias.

Original languageEnglish
Pages (from-to)124-127
Number of pages4
JournalActa Oto-Laryngologica, Supplement
Issue number523
Publication statusPublished - 1996

Fingerprint

Deoxycytidine Kinase
Immunosuppressive Agents
Deoxycytidine
Lymphocytes
Pharmaceutical Preparations
Adenosine Deaminase
Thymidine Kinase
Palatine Tonsil
Cytarabine
Enzymes
S Phase
Nucleosides
Leukemia
Nucleotides
Peptides
2'-deoxyadenosine
DNA

Keywords

  • Br-dA
  • Cladribine
  • Deoxycytidine
  • Human tonsillar lymphocytes

ASJC Scopus subject areas

  • Otorhinolaryngology

Cite this

Human tonsillar lymphocytes as targets for immunosuppressive and anticancer drugs. / Staub, M.; Sasvári, M.; Spasokukotskaja, T.; Piróth, Zs; Kazimierczuk, Z.

In: Acta Oto-Laryngologica, Supplement, No. 523, 1996, p. 124-127.

Research output: Contribution to journalArticle

Staub, M. ; Sasvári, M. ; Spasokukotskaja, T. ; Piróth, Zs ; Kazimierczuk, Z. / Human tonsillar lymphocytes as targets for immunosuppressive and anticancer drugs. In: Acta Oto-Laryngologica, Supplement. 1996 ; No. 523. pp. 124-127.
@article{5354d9390f664dfeb99bcd8fdcd5cd37,
title = "Human tonsillar lymphocytes as targets for immunosuppressive and anticancer drugs",
abstract = "As has been shown earlier by us, the metabolism of extracellular deoxycytidine (dCyd) is 2-3 times higher in follicular and in PNA+ cells than in other cells. Deoxycytidine kinase (dCK) is one of the most important target enzymes for anti-proliferative drugs such as arabinoside-cytosine (ara-C), 2-Cl-deoxyadenosine (CdA). Neither the dCK activity nor the polypeptide correlates with the S phase of the cells, as thymidine kinase (TK1) does in tonsils. The newly developed anti-leukemic drug CdA, and also BrdA, are also phosphorylated by dCK and both effectively inhibit the 3H-dThd incorporation into DNA in tonsillar lymphocytes. A new molecular mechanism has been developed for CdA; it inhibits the interconversion of dCyd into dThd nucleotides. Analysis of the pools after 3H-dCyd labeling showed a decrease of the dUMP labeling. The inhibition of dCMP deaminase by the corresponding monophosphates (Cl-dAMP) in the cells has been suggested. CdA cannot be deaminated by adenosine deaminase (ADA), thus providing a good tool to investigate the importance of that enzyme during differentiation of the lymphoid cells. Elucidation of the nucleoside metabolism during the normal differentiation process might be the only way to get information about the same pathways in malignant transformations, i.e. in leukemias.",
keywords = "Br-dA, Cladribine, Deoxycytidine, Human tonsillar lymphocytes",
author = "M. Staub and M. Sasv{\'a}ri and T. Spasokukotskaja and Zs Pir{\'o}th and Z. Kazimierczuk",
year = "1996",
language = "English",
pages = "124--127",
journal = "Acta Oto-Laryngologica, Supplement",
issn = "0365-5237",
publisher = "Taylor and Francis Ltd.",
number = "523",

}

TY - JOUR

T1 - Human tonsillar lymphocytes as targets for immunosuppressive and anticancer drugs

AU - Staub, M.

AU - Sasvári, M.

AU - Spasokukotskaja, T.

AU - Piróth, Zs

AU - Kazimierczuk, Z.

PY - 1996

Y1 - 1996

N2 - As has been shown earlier by us, the metabolism of extracellular deoxycytidine (dCyd) is 2-3 times higher in follicular and in PNA+ cells than in other cells. Deoxycytidine kinase (dCK) is one of the most important target enzymes for anti-proliferative drugs such as arabinoside-cytosine (ara-C), 2-Cl-deoxyadenosine (CdA). Neither the dCK activity nor the polypeptide correlates with the S phase of the cells, as thymidine kinase (TK1) does in tonsils. The newly developed anti-leukemic drug CdA, and also BrdA, are also phosphorylated by dCK and both effectively inhibit the 3H-dThd incorporation into DNA in tonsillar lymphocytes. A new molecular mechanism has been developed for CdA; it inhibits the interconversion of dCyd into dThd nucleotides. Analysis of the pools after 3H-dCyd labeling showed a decrease of the dUMP labeling. The inhibition of dCMP deaminase by the corresponding monophosphates (Cl-dAMP) in the cells has been suggested. CdA cannot be deaminated by adenosine deaminase (ADA), thus providing a good tool to investigate the importance of that enzyme during differentiation of the lymphoid cells. Elucidation of the nucleoside metabolism during the normal differentiation process might be the only way to get information about the same pathways in malignant transformations, i.e. in leukemias.

AB - As has been shown earlier by us, the metabolism of extracellular deoxycytidine (dCyd) is 2-3 times higher in follicular and in PNA+ cells than in other cells. Deoxycytidine kinase (dCK) is one of the most important target enzymes for anti-proliferative drugs such as arabinoside-cytosine (ara-C), 2-Cl-deoxyadenosine (CdA). Neither the dCK activity nor the polypeptide correlates with the S phase of the cells, as thymidine kinase (TK1) does in tonsils. The newly developed anti-leukemic drug CdA, and also BrdA, are also phosphorylated by dCK and both effectively inhibit the 3H-dThd incorporation into DNA in tonsillar lymphocytes. A new molecular mechanism has been developed for CdA; it inhibits the interconversion of dCyd into dThd nucleotides. Analysis of the pools after 3H-dCyd labeling showed a decrease of the dUMP labeling. The inhibition of dCMP deaminase by the corresponding monophosphates (Cl-dAMP) in the cells has been suggested. CdA cannot be deaminated by adenosine deaminase (ADA), thus providing a good tool to investigate the importance of that enzyme during differentiation of the lymphoid cells. Elucidation of the nucleoside metabolism during the normal differentiation process might be the only way to get information about the same pathways in malignant transformations, i.e. in leukemias.

KW - Br-dA

KW - Cladribine

KW - Deoxycytidine

KW - Human tonsillar lymphocytes

UR - http://www.scopus.com/inward/record.url?scp=0029657827&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029657827&partnerID=8YFLogxK

M3 - Article

C2 - 9082756

AN - SCOPUS:0029657827

SP - 124

EP - 127

JO - Acta Oto-Laryngologica, Supplement

JF - Acta Oto-Laryngologica, Supplement

SN - 0365-5237

IS - 523

ER -