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Xeroderma pigmentosum patients from the federal Republic of Germany: Decrease in post-UV colony-forming ability in 30 xeroderma pigmentosum fibroblast strains is quantitatively correlated with a decrease in DNA-incising capacity

  • Original Papers
  • Clinical Oncology or Epidemiology
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Summary

A total of 16 normal and 46 XP fibroblast strains from the Mannheim Collection were investigated for colony-forming ability following exposure to both UV light and the “UV-like” carcinogen (Ac)2ONFln. The dose-response experiments included up to 13 dose levels. The exponential segments of the curves were analysed by linear regression and the negative reciprocal of the regression coefficient (D0) was calculated for each cell strain.

For quantitating the DNA-incising capacity, DNA elution curves were determined at several UV dose levels. Plotting the initial velocities of the elution curves versus the UV dose yielded a regression line, the slope of which was used to obtain the characteristic value E0.

Comparing D0 with E0 values showed that cell strains in which colony-forming ability was reduced suffered a reduction of DNA-incising capacity of the same magnitude. There were only 3 exceptional strains in which reduction of DNA-incising capacity was less pronounced than reduction of colony-forming ability. We have previouly shown (Fischer et al. 1982) that D0 values from 27 XP strains of the Mannheim Collection were correlated with clinical symptoms. This correlation is now being extended by relating colony-forming ability to the magnitude of the DNA incision defect. From our data we conclude that the best quantitative biochemical denominator to explain the sun sensitivity of XP is that of a defective incision of UV-damaged DNA.

A considerable similarity in sensitivity towards both UV light and (Ac)2ONFln was found in 16 normal and 46 XP strains. This seems to indicate that UV-and (Ac)2ONFln-induced DNA damage are removed to a large extent by the same pathways in human fibroblasts.

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Abbreviations

XP:

xeroderma pigmentosum

(Ac)2ONFln:

N-acetoxy-2-acetylaminofluorene

UV light:

ultraviolet light

HEPES:

N-2-hydroxyethylpiperazine-N′-2-ethanesulfonic acid

ara-C:

1-β-d-arabinofuranosyl cytosine

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Authors and Affiliations

  1. Instute of Biochemistry, German Cancer Research Centre, Im Neuenheimer Feld 280, D-6900, Heidelberg, Federal Republic of Germany

    Heinz Walter Thielmann, Odilia Popanda & Susanne Friemel

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

    Lutz Edler

Authors
  1. Heinz Walter Thielmann
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  2. Lutz Edler
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  3. Odilia Popanda
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  4. Susanne Friemel
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This work was supported by the Deutsche Forschungsgemeinschaft, SFB 136

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Thielmann, H.W., Edler, L., Popanda, O. et al. Xeroderma pigmentosum patients from the federal Republic of Germany: Decrease in post-UV colony-forming ability in 30 xeroderma pigmentosum fibroblast strains is quantitatively correlated with a decrease in DNA-incising capacity. J Cancer Res Clin Oncol 109, 227–240 (1985). https://doi.org/10.1007/BF00390362

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  • DOI: https://doi.org/10.1007/BF00390362

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