MUTAGEN-INDUCED DISTURBANCES IN THE DNA OF HUMAN-LYMPHOCYTES DETECTED BY ANTI-NUCLEOSIDE ANTIBODIES

  • 1 January 1979
    • journal article
    • research article
    • Vol. 39  (9) , 3524-3530
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% (SE) of resting peripheral blood lymphocytes were immunoreactive to antinucleoside antibodies. 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 was dose dependent; up to 90% of lymphocytes could be rendered immunoreactive. Parallel studies with HeLa [human cervical carcinoma] 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 2 parameters of response to DNA damage increased in parallel. These results provide a new basis for detecting the action of alkylating mutagens on human lymphocytes in vitro or in vivo.

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