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Xeroderma pigmentosum patients from Germany: repair capacity of 45 XP fibroblast strains of the Mannheim XP Collection as measured by colony-forming ability and unscheduled DNA synthesis following treatment with methyl methanesulfonate and N-methyl-N-nitrosourea

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  • Experimental Oncology
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Summary

A total of 45 XP fibroblast strains from the Mannheim XP Collection (representatives of XP complementation groups A, C, D, E, F or G, I, and XP variants) were investigated for colony-forming ability (term: D0 after treatment with up to ten doses of the methylating carcinogen MeSO2OMe. As controls 16 fibroblast strains from normal donors were used. Except for 4 XP strains (1 from group C and 3 from group D) which, however, were borderline cases, none of the remaining 41 XP strains was found to be more sensitive than normal controls. This held true within the limits of an experimental accuracy (experimental variability of D0 values) of ±7%. When weighted means were calculated for XP complementation groups and compared with that of normal donors at a significance level of 5%, no significant difference was detected. In contrast, after exposure of 6 XP group D strains to MeNOUr, a weighted mean D0 value was obtained which was significantly decreasd by 27%. Unscheduled DNA synthesis (term: G0 which serves as a measure of excision repair) after exposure to MeNOUr was quantitatively the same (exposure to MeNOUr was quantitatively the same (experimental varability: ±8%) both in the group of normal strains and in most of the XP complementation groups. Exceptions were group E and group F (or G) which had higher, and group I which had lower repair. Analogous G0 values measured after exposure to MeSO2OMe (experimental variability: ±13%), however, differed from that of the control strains: they were lower in XP complementation groups A, D, E, F (or G), and I. However, groups A, E, F (or G), and I including only 3 individual strains or less may be considered to be possibly ill-represented. Yet, group D including 11 XP strains did show reduction of the mean G0 value by 35%. From this it is concluded that there are repair defects in XP group D strains with regrad to MeSO2OMe-induced adducts. These defects seem to be small.

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Abbreviations

XP:

xeroderma pigmentosum

MeSO2OMe:

methyl methanesulfonate

MeNOUr:

N-methyl-N-nitrosourea

Me(NO)(NO2)Gdn:

N-methyl-N′-nitro-N-nitrosoguanidine

HEPES:

N-2-hydroxyethyl-piperazine-N′-2-ethanesulfonic acid

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Authors and Affiliations

  1. Institute of Biochemistry, Information and Statistics of the German Cancer Research Centre, Im Neuenheimer Feld 280, D-6900, Heidelberg, Federal Republic of Germany

    Heinz Walter Thielmann & Susanne Friemel

  2. Institute of Documentation, Information and Statistics of the German Cancer Research Centre, Im Neuenheimer Feld 280, D-6900, Heidelberg, Federal Republic of Germany

    Lutz Edler

Authors
  1. Heinz Walter Thielmann
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  2. Lutz Edler
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  3. Susanne Friemel
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Additional information

This work was supported by the Deutsche Forschungsgemeinschaft, SFB 136

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Thielmann, H.W., Edler, L. & Friemel, S. Xeroderma pigmentosum patients from Germany: repair capacity of 45 XP fibroblast strains of the Mannheim XP Collection as measured by colony-forming ability and unscheduled DNA synthesis following treatment with methyl methanesulfonate and N-methyl-N-nitrosourea. J Cancer Res Clin Oncol 112, 245–257 (1986). https://doi.org/10.1007/BF00395919

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  • DOI: https://doi.org/10.1007/BF00395919

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