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.
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 carcinogens 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: G0) used as a measure of DNA repair synthesis. The mean experimental variability of G0 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, G0 values of the individual strains were combined to yield group-specific weighted mean G0 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 E0. The mean experimental variability of E0 of individual strains was +/- 22%. These E0 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 G0 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 G0 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 (E0) significantly diminished, although it should be noted that group sizes were only half as large as for G0 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.(ABSTRACT TRUNCATED AT 400 WORDS)
D000099:Acetoxyacetylaminofluorene / Q000627:therapeutic use; D002280:Basal Cell Carcinoma / Q000188:drug therapy / Q000235:genetics* / Q000532:radiotherapy; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000235:genetics* / Q000532:radiotherapy; D002478:Cells, Cultured; D004260:DNA Repair / Q000187:drug effects / Q000528:radiation effects; D004273:DNA, Neoplasm / Q000235:genetics; D005347:Fibroblasts; D006801:Humans; D007642:Keratosis / Q000188:drug therapy / Q000235:genetics* / Q000532:radiotherapy; D008545:Melanoma / Q000188:drug therapy / Q000235:genetics* / Q000532:radiotherapy; D008741:Methyl Methanesulfonate / Q000627:therapeutic use; D008770:Methylnitrosourea / Q000627:therapeutic use; D012878:Skin Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000532:radiotherapy; D014466:Ultraviolet Rays
D004273:DNA, Neoplasm; D000099:Acetoxyacetylaminofluorene; D008770:Methylnitrosourea; D008741:Methyl Methanesulfonate