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ABSTRACT The 1-(2-chloroethyl)-1-nitrosoureas are potent anti-cancer drugs1,2 which produce DNA inter-strand cross-links in a two-step reaction sequence. The first step was proposed to be an

addition of a chloroethyl group to a guanine-O6 position of DNA3; the second step, which occurs over a period of several hours in the absence of free drug3–6, could then form an

inter-strand cross-link by the slow reaction of the bound chloroethyl group with a nucleophilic site on the opposite DNA strand. The delay between the formation of chloroethyl monoadducts

and the formation of inter-strand cross-links allows time for a DNA repair mechanism, capable of removing the monoadducts, to prevent the cross-linking. We recently proposed this mechanism

to account for a difference in inter-strand cross-linking between a normal and a transformed human cell strain6. Day and his coworkers (see refs 7, 8 and previous paper9) found that some

human tumour cell strains (designated Mer− phenotype) are deficient in the ability to repair O6-methylguanine lesions in DNA. We therefore hypothesized that the repair function that removes

O6-methylguanine residues from DNA would also remove chloroethyl monoadducts and hence prevent chloro-ethylnitrosourea-induced inter-strand cross-linking. We now present evidence that

supports this hypothesis and indicates also that the O6-methylguanine repair confers resistance to cell killing by chloroethylnitrosourea. Access through your institution Buy or subscribe

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NEIL3-MEDIATED PROTEASOMAL DEGRADATION FACILITATES THE REPAIR OF CISPLATIN-INDUCED DNA DAMAGE IN HUMAN CELLS Article Open access 30 March 2023 DNA INTERSTRAND CROSS-LINKS INDUCED BY THE

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RESECTION Article Open access 04 August 2022 REFERENCES * Wheeler, G. P. _Handbk exp. Pharmac._ 38, 65–84 (1975). CAS  Google Scholar  * Carter, S. K. _Cancer Treat. Rep._ 60, 645–811

(1976). Google Scholar  * Kohn, K. W. _Cancer Res._ 37, 1450–1454 (1977). CAS  PubMed  Google Scholar  * Lown, J. W., McLaughlin, L. W. & Chang, Y-M. _Bioorgan. Chem._ 7, 97–110 (1978).

Article  CAS  Google Scholar  * Ewig, R. A. G. & Kohn, K. W. _Cancer Res._ 38, 3197–3203 (1978). CAS  PubMed  Google Scholar  * Erickson, L. C., Bradley, M. O., Ducore, J. M., Ewig, R.

A. G. & Kohn, K. W. _Proc. natn. Acad. Sci. U.S.A._ 77, 467–471 (1980). Article  ADS  CAS  Google Scholar  * Day, R. S. III & Ziolkowski, C. H. _Nature_ 279, 797–799 (1979). Article

  ADS  CAS  Google Scholar  * Day, R. S. III, Ziolkowski, C. H., Scudiero, D. A., Meyer, S. A. & Mattern, M. R. _Carcinogenesis_ 1, 21 (1980). Article  CAS  Google Scholar  * Day, R.S.

III _et al._ _Nature_ 288, 724–729 (1980). Article  ADS  CAS  Google Scholar  * Kohn, K. W., Erickson, L. C., Ewig, R. A. G. & Friedman, C. A. _Biochemistry_ 15, 4629–4637 (1976).

Article  CAS  Google Scholar  * Kohn, K. W. _Meth. Cancer Res._ 16, 291–345 (1979). CAS  Google Scholar  * Kohn, K. W., Ewig, R. A. G., Erickson, L. C. & Zwelling, L. A. in _A Laboratory

Manual of Research Procedures_ (eds Friedberg, E. C. & Hanawalt, P. C.) (Dekker, New York, in the press). * Robins, P. & Cairns, J. _Nature_ 280, 74–76 (1979). Article  ADS  CAS 

Google Scholar  * Karran, P. & Lindahl, T. _Nature_ 280, 76–77 (1979). Article  ADS  CAS  Google Scholar  * Renard, A. & Verly, W. G. _FEBS Lett._ 114, 98–102 (1980). Article  CAS 

Google Scholar  Download references AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Laboratory of Molecular Pharmacology, Developmental Therapeutics Program, Division of Cancer Treatment,

National Cancer Institute, National Institutes of Health, Bethesda, Maryland, 20205 Leonard C. Erickson, Guy Laurent, Nancy A. Sharkey & Kurt W. Kohn Authors * Leonard C. Erickson View

author publications You can also search for this author inPubMed Google Scholar * Guy Laurent View author publications You can also search for this author inPubMed Google Scholar * Nancy A.

Sharkey View author publications You can also search for this author inPubMed Google Scholar * Kurt W. Kohn View author publications You can also search for this author inPubMed Google

Scholar RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Erickson, L., Laurent, G., Sharkey, N. _et al._ DNA cross-linking and monoadduct repair in

nitrosourea-treated human tumour cells. _Nature_ 288, 727–729 (1980). https://doi.org/10.1038/288727a0 Download citation * Received: 15 July 1980 * Accepted: 27 October 1980 * Issue Date: 18

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