Increased bleomycin-induced chromosome damage in lymphocytes of patients with common variable immunodeficiency indicates an involvement of chromosomal instability in their cancer predisposition

Abstract

To study mutagen-induced chromosome instability in cancer disposition, late S and G2 lymphocytes of 15 patients with common variable immunodeficiency and 14 healthy controls were exposed to bleomycin in vitro. The groups did not differ in the frequency of spontaneous chromosome aberrations. In bleomycin-treated samples we found higher numbers of break events per cell and increased frequency of cells with aberrations compared to the control group. A slightly reduced breakage of chromosome group D was noted in patients. These results support the hypothesis that a higher incidence of cancer in patients with genetically determined immunodeficiencies may be explained by an increased mutagen-induced chromosome instability in at least some of them.

The Inherited Basis of Human Radiosensitivity

“…3); CHK2 (¾ RAD52) (Li-Fraumeni syndrome) (32,93), Ligase IV, XRCC4, DNA-PK c s , and Ku genes (94 -96). RS has also been observed in some patients with common variable immunode ciency (97,98). These observations of a concordance of immunode ciency with RS, and cancer, suggest common underlying mechanisms, perhaps via ATM-dependent phosphorylation of key components of these common pathways or repair complexes.…”

Bleomycin-induced chromosomal damage in tuberous sclerosis

“…It is likely that chromosomal sensitivity to mutagens plays an important role in carcinogenesis of organs and tissues that have direct contact with the external environment, such as respiratory, digestive, and integumentary systems (Hsu et al, 1989). Furthermore, a similar increase in number of chromosomal aberrations was also found in some heritable cancer-prone conditions after X-irradiation or BLM treatment in vitro (Parshad et al, 1983;Sanford et al, 1987;Vorechovsky et al, 1989b). It appears that this increased chromosomal damage results from deficient mechanisms of DNA repair (Gantt et al, 1987).…”

“…To minimize the proportion of the cells exposed in the S phase of the cell cycle we shortened the time of exposure to BLM from 5 to 4 hr, which we had used pre-viously (Vorechovsky et al, 1989b). We obtained a comparable number chromosome-type aberrations (4.0~o in the patients and 4.1 ~o in controls, the difference being negligible).…”

Persistence of Chromosomal Aberrations in Blood Lymphocytes of Testicular Cancer Patients

“…Chromosome aberrations were recorded in 100 cells per person according to WHO recommendations [3] and 50 cells were analysed for SCE frequency. Chromatid breaks were counted as single-break events, and chromosome type aberrations were considered as twobreak events [17]. Cells with more than 5 aberrations were cal culated as cells with multiple aberrations.…”