Pyrimethamine-induced alterations in human lymphocytes in vitro. Mechanisms and reversal of the effect

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Pyrimethamine-induced alterations in human lymphocytes in vitro. Mechanisms and reversal of the effect. / Bygbjerg, Ib Christian.

In: Acta pathologica, microbiologica, et immunologica Scandinavica. Section C, Immunology, Vol. 93, No. 4, 01.08.1985, p. 183-8.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Bygbjerg, IC 1985, 'Pyrimethamine-induced alterations in human lymphocytes in vitro. Mechanisms and reversal of the effect', Acta pathologica, microbiologica, et immunologica Scandinavica. Section C, Immunology, vol. 93, no. 4, pp. 183-8.

APA

Bygbjerg, I. C. (1985). Pyrimethamine-induced alterations in human lymphocytes in vitro. Mechanisms and reversal of the effect. Acta pathologica, microbiologica, et immunologica Scandinavica. Section C, Immunology, 93(4), 183-8.

Vancouver

Bygbjerg IC. Pyrimethamine-induced alterations in human lymphocytes in vitro. Mechanisms and reversal of the effect. Acta pathologica, microbiologica, et immunologica Scandinavica. Section C, Immunology. 1985 Aug 1;93(4):183-8.

Author

Bygbjerg, Ib Christian. / Pyrimethamine-induced alterations in human lymphocytes in vitro. Mechanisms and reversal of the effect. In: Acta pathologica, microbiologica, et immunologica Scandinavica. Section C, Immunology. 1985 ; Vol. 93, No. 4. pp. 183-8.

Bibtex

@article{936d685840df415bbd53debbf86486f9,
title = "Pyrimethamine-induced alterations in human lymphocytes in vitro. Mechanisms and reversal of the effect",
abstract = "It has previously been shown that the antiprotozoal drug pyrimethamine (PYR) in concentrations corresponding to those obtained in clinical practice temporarily suppressed the proliferation of phytohaemagglutinin (PHA-) stimulated human lymphocytes in vitro; 10-fold higher concentrations permanently suppressed PHA-stimulated cells, as indicated by decreased numbers of cells and DNA synthesis. In the present study, it was found that the 3H-deoxyuridine incorporation in PHA-stimulated lymphocytes was suppressed by PYR, and that PYR caused defective deoxyuridine suppression of 14C-thymidine incorporation. The effects of PYR were completely corrected by low concentrations of folinic acid and high concentrations of folic acid, indicating that the basic mechanism of action of PYR is competitive blocking of dihydrofolate reductase. However, the effect of PYR was poorly corrected by exogenous thymidine; therefore, reduced thymidylate synthesis cannot be the sole consequence of PYR exposure. It is suggested that an additional folate-dependent factor plays an important role in the antimitotic activity of PYR on lymphocytes.",
keywords = "DNA, Deoxyuracil Nucleotides, Humans, Lymphocyte Activation, Lymphocytes, Pyrimethamine, Thymidine, Thymidine Kinase",
author = "Bygbjerg, {Ib Christian}",
year = "1985",
month = aug,
day = "1",
language = "English",
volume = "93",
pages = "183--8",
journal = "Acta Pathologica Microbiologica et Immunologica Scandinavica - Section C Immunology",
issn = "0108-0202",
publisher = "Wiley-Blackwell",
number = "4",

}

RIS

TY - JOUR

T1 - Pyrimethamine-induced alterations in human lymphocytes in vitro. Mechanisms and reversal of the effect

AU - Bygbjerg, Ib Christian

PY - 1985/8/1

Y1 - 1985/8/1

N2 - It has previously been shown that the antiprotozoal drug pyrimethamine (PYR) in concentrations corresponding to those obtained in clinical practice temporarily suppressed the proliferation of phytohaemagglutinin (PHA-) stimulated human lymphocytes in vitro; 10-fold higher concentrations permanently suppressed PHA-stimulated cells, as indicated by decreased numbers of cells and DNA synthesis. In the present study, it was found that the 3H-deoxyuridine incorporation in PHA-stimulated lymphocytes was suppressed by PYR, and that PYR caused defective deoxyuridine suppression of 14C-thymidine incorporation. The effects of PYR were completely corrected by low concentrations of folinic acid and high concentrations of folic acid, indicating that the basic mechanism of action of PYR is competitive blocking of dihydrofolate reductase. However, the effect of PYR was poorly corrected by exogenous thymidine; therefore, reduced thymidylate synthesis cannot be the sole consequence of PYR exposure. It is suggested that an additional folate-dependent factor plays an important role in the antimitotic activity of PYR on lymphocytes.

AB - It has previously been shown that the antiprotozoal drug pyrimethamine (PYR) in concentrations corresponding to those obtained in clinical practice temporarily suppressed the proliferation of phytohaemagglutinin (PHA-) stimulated human lymphocytes in vitro; 10-fold higher concentrations permanently suppressed PHA-stimulated cells, as indicated by decreased numbers of cells and DNA synthesis. In the present study, it was found that the 3H-deoxyuridine incorporation in PHA-stimulated lymphocytes was suppressed by PYR, and that PYR caused defective deoxyuridine suppression of 14C-thymidine incorporation. The effects of PYR were completely corrected by low concentrations of folinic acid and high concentrations of folic acid, indicating that the basic mechanism of action of PYR is competitive blocking of dihydrofolate reductase. However, the effect of PYR was poorly corrected by exogenous thymidine; therefore, reduced thymidylate synthesis cannot be the sole consequence of PYR exposure. It is suggested that an additional folate-dependent factor plays an important role in the antimitotic activity of PYR on lymphocytes.

KW - DNA

KW - Deoxyuracil Nucleotides

KW - Humans

KW - Lymphocyte Activation

KW - Lymphocytes

KW - Pyrimethamine

KW - Thymidine

KW - Thymidine Kinase

M3 - Journal article

C2 - 4050444

VL - 93

SP - 183

EP - 188

JO - Acta Pathologica Microbiologica et Immunologica Scandinavica - Section C Immunology

JF - Acta Pathologica Microbiologica et Immunologica Scandinavica - Section C Immunology

SN - 0108-0202

IS - 4

ER -

ID: 33891819