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Inhibition ofO 6-alkylguanine-DNA alkyltransferase and DNase I activities in vitro by some alkylating substances and antineoplastic agents

  • Original Papers
  • Experimental Oncology
  • Published:
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Summary

The specificities of the DNA repair enzymeO 6-alkylguanine-DNA alkyltransferase from brain and liver cells of the chick embryo and of DNase I were demonstrated in vitro by their response to substrate DNA pretreated with monofunctional alkylating agents of differentO 6-guanine alkylating ability and some antineoplastic agents. Treatment of DNA with ethidium bromide, Hoechst 33258, doxorubicin, Fe2+/bleomycin, and suramin resulted in a dose-dependent diminution of alkyltransferase activity (DE50 ≈ 5 μg/ml, 15 μg/ml, 5 μg/ml, 5 μg/ml, 100 μg/ml, respectively). Apart from bleomycin, comparable results were obtained with DNase I. Thermal denaturation of the substrate DNA reduced both alkyltransferase and DNase I activity. No effect was seen with X-irradiation. Cisplatin decreased only DNase I activity. Some topoisomerase II and/or gyrase inhibitors remained without significant effects on the alkyltransferase reaction whereas DNA catabolism by DNase I was diminished in a dose-dependent manner (DE50 between 6.5 and 19 μg/ml).

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Abbreviations

AT:

alkyltransferase

BB:

bisbenzimide

EB:

ethidium bromide

DOX:

doxorubicin

CDDP:

cis-diamminedichloroplatinum (II)

MMS:

methylmethanesulphonate

EMS:

ethylmethanesulphonate

MNU:

methylnitrosourea

ENU:

ethylnitrosourea

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Authors and Affiliations

  1. Institute of Pharmacology, Toxicology and Pharmacy, University of Munich, Germany

    A. Link & K. Tempel

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  1. A. Link
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  2. K. Tempel
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Link, A., Tempel, K. Inhibition ofO 6-alkylguanine-DNA alkyltransferase and DNase I activities in vitro by some alkylating substances and antineoplastic agents. J Cancer Res Clin Oncol 117, 549–555 (1991). https://doi.org/10.1007/BF01613287

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  • DOI: https://doi.org/10.1007/BF01613287

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