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DNA repair synthesis in fibroblast strains from patients with actinic keratosis, squamous cell carcinoma, basal cell carcinoma, or malignant melanoma after treatment with ultraviolet light, N-acetoxy-2-acetyl-aminofluorene, methyl methanesulfonate, and N-methyl-N-nitrosourea

  • Original Papers
  • Clinical Oncology or Epidemiology
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Summary

Fibroblast strains derived from skin biopsies of patients with actinic keratosis (6), malignant melanoma (18), squamous cell carcinoma (11), and basal cell carcinoma (12) were investigated for DNA repair synthesis, with 16 fibroblast strains for normal donors as controls. Cells were exposed to UV light, the “UV-like” carcinogen (Ac)2ONFln, and the methylating carcinogenes MeSO2OMe and MeNOUr. Dose-response experiments, which included 10 dose levels, were performed, the data analyzed by linear regression, and the slope of the regression line (term: G 0) used as a measure of DNA repair synthesis. The mean experimental variability of G 0 of individual fibroblast strains was 9.5%–15.4%, depending upon exposure. For comparison of all cell strains belonging to the same skin malignancy group with those of the control group, G 0 values of the individual strains were combined to yield group-specific weighted mean G 0 values.

In addition, the capacity to incise UV-damaged DNA was measured in 24 cell strains from patients with skin tumors using the alkaline elution technique. For quantitating DNA-incising capacity, the initial velocities of the elution curves were plotted versus the UV dose, and the slope of the resulting regression line was used to obtain the characteristic value E 0. The mean experimental variability of E 0 of individual strains was ±22%. These E 0 values were combined to yield weighted mean values of groups.

The fibroblast strains in the groups of patients with actinic keratosis and malignant melanoma were found to have normal mean G 0 values when DNA repair synthesis was challenged with UV light or one of the three carcinogens. However, the squamous cell carcinoma group exhibited significantly lower mean G 0 values after treatment with UV light (82% that of normal donors), (Ac)2ONFln (70%), MeSO2OMe (70%), and MeNOUr (69%). The basal cell carcinoma group showed significantly diminished repair synthesis upon treatment with UV light (81% that of normal donors) and MeSO2OMe (67%). In contrast to these findings, in no skin malignancy group was post UV DNA-incising capacity (E 0) significantly diminished, although it should be noted that group sizes were only half as large as for G 0 determinations.

These data may be interpreted as indicating that DNA excision repair is impaired in fibroblast strains from patients with squamous cell carcinoma and — to a lesser extent — basal cell carcinoma. This deficiency seems to pertain to several DNA repair mechanisms, as excision of both alkylation and UV-induced damage is involved. Although the repair impairments are statistically significant, the relative risks at which the investigated patients are do not seem to be high enough as to be of immediate practical value. Our results indicate further studies would be useful.

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Abbreviations

XP:

xeroderma pigmentosum

UV light:

ultraviolet light

UVB:

UV light with the wavelength from 290 nm to 320 nm

(Ac)2ONFln:

N-acetoxy-2-acetylaminofluorene

MeSO2OMe:

methyl methanesulfonate

MeNOUr:

N-methyl-N-nitrosourea

ara-C:

1-β-d-arabinofuranosyl cytosine

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Authors and Affiliations

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

    Heinz Walter Thielmann & Max Roland Burkhardt

  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

  3. Department of Dermatology, Mannheim Medical School, Theodor-Kutzer-Ufer, D-6800, Mannheim, Federal Republic of Germany

    Ernst Gustav Jung

Authors
  1. Heinz Walter Thielmann
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  2. Lutz Edler
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  3. Max Roland Burkhardt
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  4. Ernst Gustav Jung
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Dedicated to Professor E. Hecker on the occasion of his 60th birthday

This work was supported by the Deutsche Forschungsgemeinschaft, SFB 136

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Thielmann, H.W., Edler, L., Burkhardt, M.R. et al. DNA repair synthesis in fibroblast strains from patients with actinic keratosis, squamous cell carcinoma, basal cell carcinoma, or malignant melanoma after treatment with ultraviolet light, N-acetoxy-2-acetyl-aminofluorene, methyl methanesulfonate, and N-methyl-N-nitrosourea. J Cancer Res Clin Oncol 113, 171–186 (1987). https://doi.org/10.1007/BF00391441

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  • DOI: https://doi.org/10.1007/BF00391441

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