Fibroblast cultures of patients with basal cell epithelioma exhibit a normal sensitivity to the genotoxic effect of ultraviolet irradiation

Fibroblast cultures of 16 basal cell epithelioma (basalioma, BCE) patients with an unusu- ally young age at onset of disease (29-51 years; 42.5 +-7.04), and healthy normal controls (27-55 years; 40.73 +-9.52) were studied for chromosome instability induced by ultraviolet rays (UV). We used an UV source that emitted predominantly UV-A and UV-B at an intensity of 375 J/m2 and evaluated the induction of micronuclei (MN) and sister chromatid exchange (SCE). Young basalioma patients and normal controls showed no significant differences in MN and SCE frequencies, neither with respect to spontaneous nor to UV-induced values (MN spontaneous: 10.80 +- 5.65 vs.11.32 +- 8.21; UV-induced increase: 7.36 +- 4.40 vs. 9.93 +- 7.55; SCE spontaneous: 10.28 +- 1.61 vs. 10.72 +- 1.09; UV-induced increase: 7,30 +-2.19 vs. 7.55 +-2,14). We conclude from these data that an enhanced UV sensitivity as observed in cells from patients with cutaneous malignant melanoma and xeroderma pigmentosum is not a constitutive risk factor in basalioma patients

Increased spontaneous formation of micronuclei in cultured fibroblasts of first-degree relatives of familial melanoma patients

The phenomenon of spontaneous increased micronuclei and enhanced UV-sensitivity, which is known for familial cutaneous malignant melanoma (CMM) patients, could be demonstrated again in fibroblasts of 17 familial CMM patients. In order to determine if close relatives of familial CMM patients show both a comparable spontaneous chromosomal instability and enhanced UV-sensitivity, cultured fibroblasts of 24 healthy, first-degree relatives of patients with familial malignant melanoma were investigated. The cytokinesis-block micronucleous technique was used to detect enhanced chromosomal instability. Fibroblasts of the investigated relatives showed a significantly increased spontaneous formation of micronuclei, in comparison to 19 healthy controls, but no enhanced UV-sensitivity was evident. We conclude that chromosomal instability might be a hereditary trait and a causative factor in developing familial malignant melanoma. This supports the concept of a genetic predisposition to familial CMM and may help to identify high-risk family members at a cytogenetic level in addition to the common clinicopathological traits. (C) Elsevier Science Inc., 1997

Constitutively increased micronuclei are predominantly caused by acentric fragments

The frequency of kinetochore (centromere)-positive micronuclei (MN) was determined in 32 fibroblast cell lines. We tested 16 probands with spontaneously high MN levels (greater than or equal to 20 MN/500 cells (4%] and 8 probands (controls) with low MN levels (less than or equal to 13 MN/500 cells (2.6%]. To study whether the elevation of MN levels is due to increased chromosomal breakage we used the antikinetochore antibody fluorescent staining method. Probands with spontaneously high MN had kinetochore-positive MN increased by a factor 2.1 compared to the controls whereas the kinetochore-negative MN were increased by a factor 6.14. This shows that spontaneous elevation of MN is mainly caused by increased chromosomal breakage and only in a minor proportion by chromosome segregation errors as a consequence of spindle defects