Latent chromosomal instability in cancer patients

Abstract

There is increasing evidence that, similar to what is found with other genetic disorders, genomic instability is one of the most general features of cancer. Different forms of manifestation including latent instability have been suggested. To recognize latent chromosomal instability we treated lymphocyte cultures of cancer patients and healthy persons with caffeine, two different doses of bleomycin, and a combination of bleomycin and caffeine. The preliminary results demonstrate that, although the rate of spontaneous chromosomal aberrations is similar in both investigated groups, the lymphocytes of cancer patients display an increased susceptibility to treatment with bleomycin and caffeine. In distinguishing between healthy individuals and those with malignancy, treatment with 30 micrograms/ml bleomycin appears to be most important. Values of chromosomal change above one break per cell, more than 45% cells with chromosomal alterations, and more that two cells with chromosomal rearrangements are suggestive of malignancy. These findings imply that treatment of lymphocyte cultures with bleomycin and caffeine could be a useful assay for monitoring chromosomal instability, and thus detecting a predisposition to malignant disease. In this respect further investigations on a greater amount of material should be performed.

Chromosomal instability in cancer patients

“…The Nordic Study Group (1990) and Hagman et al (1994) have reported a significant increase of cancer incidence in subjects with the highest level of chro- Hsu et al (1981) in the cultured peripheral blood lymphocytes of patients with multiple endocrine adenomatosis. The literature and our results contradict the findings of Tzancheva and Komitowski (1997). They claim that the rate of spontaneous chromosomal aberrations is similar in cancer patients and healthy persons and that the lymphocytes of cancer patients display an increased susceptibility to treatment with bleomysin and caffeine.…”

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Tzancheva and Komitowski (1997) recently reported data on a latent chromosomal instability (induced by bleomycin and caffeine) in 15 patients with different types of cancer, viz. urological cancer, testis seminoma and colon carcinoma.

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“…The average age of the cancer cases was 49.83±3.31 years (mean±SD), of the APC cases 39.2±2.74 years and of the controls 45.3±4.2 years. We applied the same routine cytogenetic method as Tzancheva and Komitowski (1997). Peripheral blood lymphocytes were cultured for 72 h in medium RPMI with 15% fetal calf serum following standard procedure.…”

No latent chromosome damage in oxygen-exposed premature neonates

“…From the short-term (50 h) cultures, conventionally prepared slides were Giemsa stained without banding procedures. Parallel cultures were treated for the final 5 h with bleomycin in a final concentration of 30 µg/ml, as described by Tzancheva and Komitowski (1997). From both untreated and bleomycintreated preparations, on each occasion 100 mitoses were analyzed for anomalies as follows: chromatid and chromosome breaks, other structural aberrations, pulverization, and premature centromere divisions (PCDs).…”

Comments on the letter of Toncheva and Nacheva concerning our paper “Latent chromosomal instability in cancer patients”

“…An important aspect of our study is, however, the definition of break events that allow the discrimination of healthy controls from cancer patients and the detection of persons at risk when clastogenic treatment is applied: notably, the healthy person who revealed a higher number of breaks (above 1.00 b/c) after treatment of lymphocytes with bleomycin ( Fig. 1, p 49 of our publication, Tzancheva and Komitowski 1997) and who developed Hodgkin lymphoma 6 months ago, 2 years after the cytogenetic evaluation.…”