Mutagen-induced disturbances in the DNA of human lymphocytes detected by antinucleoside antibodies

R. Bases, Arye Rubinstein, A. Kadish, F. Mendez, D. Wittner, F. Elequin, D. Liebeskind

Research output: Contribution to journalArticle

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Abstract

The alkylating mutagens N-methyl-N'-nitro-N-nitrosoguanidine, methyl methanesulfonate, and N-nitroso-methylurea induced immunoreactivity to antinucleoside antibodies in human peripheral blood lymphocytes in vitro. This could also be detected in lymphocytes taken from a patient soon after i.v. administration of cyclophosphamide. The immunoreactivity response, which indicates denatured DNA or DNA single-strand breaks, was scored by immunofluorescent or immunoperoxidase techniques. Examination of blood from 10 normal subjects showed that 32 ± 4% (S.E) of resting peripheral blood lymphocytes were immunoreactive to antinucleoside antibodies. We have shown that these naturally occurring immunoreactive lymphocytes are largely accounted for by a subpopulation of thymus-derived lymphocytes bearing the Fc receptor for immunoglobulin M. The presence of these cells did not interfere with the use of peripheral blood lymphocytes for in vitro measurement of additional immunoreactivity caused by alkylating mutagens. The response proved to be dose dependent; up to 90% of lymphocytes could be rendered immunoreactive. Parallel studies with HeLa cells showed a similar dose-response relationship between mutagen action and immunoreactivity. With some agents, the immunoreactivity technique detected effects at lower concentrations than could be detected by HeLa cell survival studies. With N-nitrosomethylurea, measurement of DNA repair synthesis by [ 3H]thymidine autoradiography showed that in HeLa cells these two parameters of response to DNA damage increased in parallel. Our results provide a new basis for detecting the action of alkylating mutagens on human lymphocytes in vitro or in vivo.

Original languageEnglish (US)
Pages (from-to)3524-3530
Number of pages7
JournalCancer Research
Volume39
Issue number9
StatePublished - 1979

Fingerprint

Mutagens
Lymphocytes
Antibodies
DNA
HeLa Cells
Methyl Methanesulfonate
Immunoglobulin Fc Fragments
Methylnitrosourea
Single-Stranded DNA Breaks
Methylnitronitrosoguanidine
Fc Receptors
Autoradiography
Immunoenzyme Techniques
DNA Repair
Cyclophosphamide
Thymidine
Thymus Gland
DNA Damage
Immunoglobulin M
Cell Survival

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Bases, R., Rubinstein, A., Kadish, A., Mendez, F., Wittner, D., Elequin, F., & Liebeskind, D. (1979). Mutagen-induced disturbances in the DNA of human lymphocytes detected by antinucleoside antibodies. Cancer Research, 39(9), 3524-3530.

Mutagen-induced disturbances in the DNA of human lymphocytes detected by antinucleoside antibodies. / Bases, R.; Rubinstein, Arye; Kadish, A.; Mendez, F.; Wittner, D.; Elequin, F.; Liebeskind, D.

In: Cancer Research, Vol. 39, No. 9, 1979, p. 3524-3530.

Research output: Contribution to journalArticle

Bases, R, Rubinstein, A, Kadish, A, Mendez, F, Wittner, D, Elequin, F & Liebeskind, D 1979, 'Mutagen-induced disturbances in the DNA of human lymphocytes detected by antinucleoside antibodies', Cancer Research, vol. 39, no. 9, pp. 3524-3530.
Bases, R. ; Rubinstein, Arye ; Kadish, A. ; Mendez, F. ; Wittner, D. ; Elequin, F. ; Liebeskind, D. / Mutagen-induced disturbances in the DNA of human lymphocytes detected by antinucleoside antibodies. In: Cancer Research. 1979 ; Vol. 39, No. 9. pp. 3524-3530.
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