Potentiation by 1-α,25-dihydroxyvitamin D3 of cytotoxicity to HL-60 cells produced by cytarabine and hydroxyurea

George Studzinski, A. K. Bhandal, Z. S. Brelvi

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

A short (4-hr) exposure to 1-4 x 10-7 M 1,25-dihydroxyvitamin D3 [(1,25(OH)2D3); 1-α,25-dihydroxycholecalciferol] induced transient differentiation in a clone (R2AB2) of human promyelocytic leukemia cells (HL-60) but caused no permanent growth impairment and no detectable cytotoxicity. This treatment with 1,25(OH)2D3 also produced an inhibition of DNA synthesis that was promptly reversed when 1,25(OH)2D3 was removed. When such treatment with 1,25(OH)2D3 immediately followed a sublethal exposure to drugs that inhibit DNA synthesis, including the cancer chemotherapeutic agents cytarabine and hydroxyurea, the proportion of HL-60 cells lethally damaged was increased. This finding was demonstrated by morphologic evidence of cell damage and disintegration, an increased permeability to trypan blue, loss of cells from culture, and a reduced clonogenic potential of the treated cells. Exposure to 1,25(OH)2D3 before treatment with a cytotoxic agent had a slightly protective rather than a damaging effect. These observations suggest that the presence of 1,25(OH)2D3 markedly reduces the capacity of HL-60 cells to repair DNA damage or to reduce the intracellular concentration of cytotoxic agents.

Original languageEnglish (US)
Pages (from-to)641-648
Number of pages8
JournalJournal of the National Cancer Institute
Volume76
Issue number4
DOIs
StatePublished - Jan 1 1986

Fingerprint

Hydroxyurea
Calcitriol
HL-60 Cells
Cytarabine
Cytotoxins
Trypan Blue
DNA
DNA Damage
Permeability
Leukemia
Clone Cells
Cell Culture Techniques
Growth
Pharmaceutical Preparations
Neoplasms

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

@article{3f933cde5d7c47a49315babeb0e03794,
title = "Potentiation by 1-α,25-dihydroxyvitamin D3 of cytotoxicity to HL-60 cells produced by cytarabine and hydroxyurea",
abstract = "A short (4-hr) exposure to 1-4 x 10-7 M 1,25-dihydroxyvitamin D3 [(1,25(OH)2D3); 1-α,25-dihydroxycholecalciferol] induced transient differentiation in a clone (R2AB2) of human promyelocytic leukemia cells (HL-60) but caused no permanent growth impairment and no detectable cytotoxicity. This treatment with 1,25(OH)2D3 also produced an inhibition of DNA synthesis that was promptly reversed when 1,25(OH)2D3 was removed. When such treatment with 1,25(OH)2D3 immediately followed a sublethal exposure to drugs that inhibit DNA synthesis, including the cancer chemotherapeutic agents cytarabine and hydroxyurea, the proportion of HL-60 cells lethally damaged was increased. This finding was demonstrated by morphologic evidence of cell damage and disintegration, an increased permeability to trypan blue, loss of cells from culture, and a reduced clonogenic potential of the treated cells. Exposure to 1,25(OH)2D3 before treatment with a cytotoxic agent had a slightly protective rather than a damaging effect. These observations suggest that the presence of 1,25(OH)2D3 markedly reduces the capacity of HL-60 cells to repair DNA damage or to reduce the intracellular concentration of cytotoxic agents.",
author = "George Studzinski and Bhandal, {A. K.} and Brelvi, {Z. S.}",
year = "1986",
month = "1",
day = "1",
doi = "10.1093/jnci/76.4.641",
language = "English (US)",
volume = "76",
pages = "641--648",
journal = "Journal of the National Cancer Institute",
issn = "0027-8874",
publisher = "Oxford University Press",
number = "4",

}

Potentiation by 1-α,25-dihydroxyvitamin D3 of cytotoxicity to HL-60 cells produced by cytarabine and hydroxyurea. / Studzinski, George; Bhandal, A. K.; Brelvi, Z. S.

In: Journal of the National Cancer Institute, Vol. 76, No. 4, 01.01.1986, p. 641-648.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Potentiation by 1-α,25-dihydroxyvitamin D3 of cytotoxicity to HL-60 cells produced by cytarabine and hydroxyurea

AU - Studzinski, George

AU - Bhandal, A. K.

AU - Brelvi, Z. S.

PY - 1986/1/1

Y1 - 1986/1/1

N2 - A short (4-hr) exposure to 1-4 x 10-7 M 1,25-dihydroxyvitamin D3 [(1,25(OH)2D3); 1-α,25-dihydroxycholecalciferol] induced transient differentiation in a clone (R2AB2) of human promyelocytic leukemia cells (HL-60) but caused no permanent growth impairment and no detectable cytotoxicity. This treatment with 1,25(OH)2D3 also produced an inhibition of DNA synthesis that was promptly reversed when 1,25(OH)2D3 was removed. When such treatment with 1,25(OH)2D3 immediately followed a sublethal exposure to drugs that inhibit DNA synthesis, including the cancer chemotherapeutic agents cytarabine and hydroxyurea, the proportion of HL-60 cells lethally damaged was increased. This finding was demonstrated by morphologic evidence of cell damage and disintegration, an increased permeability to trypan blue, loss of cells from culture, and a reduced clonogenic potential of the treated cells. Exposure to 1,25(OH)2D3 before treatment with a cytotoxic agent had a slightly protective rather than a damaging effect. These observations suggest that the presence of 1,25(OH)2D3 markedly reduces the capacity of HL-60 cells to repair DNA damage or to reduce the intracellular concentration of cytotoxic agents.

AB - A short (4-hr) exposure to 1-4 x 10-7 M 1,25-dihydroxyvitamin D3 [(1,25(OH)2D3); 1-α,25-dihydroxycholecalciferol] induced transient differentiation in a clone (R2AB2) of human promyelocytic leukemia cells (HL-60) but caused no permanent growth impairment and no detectable cytotoxicity. This treatment with 1,25(OH)2D3 also produced an inhibition of DNA synthesis that was promptly reversed when 1,25(OH)2D3 was removed. When such treatment with 1,25(OH)2D3 immediately followed a sublethal exposure to drugs that inhibit DNA synthesis, including the cancer chemotherapeutic agents cytarabine and hydroxyurea, the proportion of HL-60 cells lethally damaged was increased. This finding was demonstrated by morphologic evidence of cell damage and disintegration, an increased permeability to trypan blue, loss of cells from culture, and a reduced clonogenic potential of the treated cells. Exposure to 1,25(OH)2D3 before treatment with a cytotoxic agent had a slightly protective rather than a damaging effect. These observations suggest that the presence of 1,25(OH)2D3 markedly reduces the capacity of HL-60 cells to repair DNA damage or to reduce the intracellular concentration of cytotoxic agents.

UR - http://www.scopus.com/inward/record.url?scp=0022590635&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0022590635&partnerID=8YFLogxK

U2 - 10.1093/jnci/76.4.641

DO - 10.1093/jnci/76.4.641

M3 - Article

C2 - 3457201

AN - SCOPUS:0022590635

VL - 76

SP - 641

EP - 648

JO - Journal of the National Cancer Institute

JF - Journal of the National Cancer Institute

SN - 0027-8874

IS - 4

ER -