Chromosomal aberrations in peripheral lymphocytes of train engine drivers.

Studies of Swedish railway employees have indicated that railroad engine drivers have an increased cancer morbidity and incidence of chronic lymphatic leukemia. The drivers are exposed to relatively high magnetic fields (MF), ranging from a few to over a hundred microT. Although the possible genotoxic potential of MF is unclear, some earlier studies have indicated that occupational exposure to MF may increase chromosome aberrations in blood lymphocytes.

Cancer predictive value of cytogenetic markers used in occupational health surveillance programs.

It has not previously been clear whether cytogenetic biomarkers in healthy subjects will predict cancer. Earlier analyses of a Nordic and an Italian cohort indicated predictivity for chromosomal aberrations (CAS) but not for sister chromatid exchanges (SCES). A pooled analysis of the updated cohorts, forming a joint study base of 5271 subjects, will now be performed, allowing a more solid evaluation.

Cancer predictive value of cytogenetic markers used in occupational health surveillance programs: a report from an ongoing study by the European Study Group on Cytogenetic Biomarkers and Health.

The cytogenetic endpoints in peripheral blood lymphocytes: chromosomal aberrations (CA), sister chromatid exchange (SCE) and micronuclei (MN) are established biomarkers of exposure for mutagens or carcinogens in the work environment. However, it is not clear whether these biomarkers also may serve as biomarkers for genotoxic effects which will result in an enhanced cancer risk. In order to assess this problem, Nordic and Italian cohorts were established, and preliminary results from these two studies indicated a predictive value of CA frequency for cancer risk, whereas no such associations were observed for SCE or MN.

Prognostic impact of bone marrow karyotype in childhood acute lymphoblastic leukaemia: Swedish experiences 1986-91.

The prognostic value of cytogenetic classification in acute lymphoblastic leukaemia (ALL) was evaluated in Swedish children below 16 years of age (n = 372) diagnosed between 1986 and 1991. A bone marrow karyotype was obtained in 281 cases, of which 149 (53%) showed clonal abnormalities. Event-free survival (p-EFS) was 0.

Chromosomal changes in rheumatoid arthritis patients treated with CPH82.

Chromosomal changes were assessed in 19 patients with rheumatoid arthritis (RA) treated with CPH82, a benzylidated podophyllotoxin glycoside, for up to one year. The frequency of chromosomal aberrations (CA) and sister chromatid exchanges (SCE) in peripheral lymphocytes increased significantly after 12 weeks of treatment and remained elevated after 48 weeks treatment in peripheral lymphocytes. The number of CA and SCE were significantly increased in CPH82 treated patients compared with the RA patients treated with other disease modifying anti-rheumatic drug (sulphasalazine, gold, D-penicillamine, azathioprine, methotrexate, cyclophosphamide).

Myelodysplastic syndromes--a population-based study on transformation and survival.

A retrospective analysis was done on 113 patients (median age 73 years) with myelodysplastic syndromes (MDS), consecutively diagnosed at our center during a 10-year period. Patients with refractory anemia (RA) and refractory anemia with ringed sideroblasts (RARS) had significantly longer survival than patients with refractory anemia with excess blasts (RAEB), chronic myelomonocytic leukemia (CMML) or refractory anemia with excess blasts in transformation (RAEB-T). Thirty-seven patients (33%) subsequently developed acute myelogenous leukemia (AML).

Cancer risk in humans predicted by increased levels of chromosomal aberrations in lymphocytes: Nordic study group on the health risk of chromosome damage.

Cytogenetic assays in peripheral blood lymphocytes (PBL) have been used extensively to survey the exposure of humans to genotoxic agents. The conceptual basis for this has been the hypothesis that the extent of genetic damage in PBL reflects critical events for carcinogenic processes in target tissues. Until now, no follow-up studies have been performed to assess the predictive value of these methods for subsequent cancer risk.

Simultaneous immunoglobulin/T-cell receptor gene rearrangements and multiclonality in childhood acute lymphoblastic leukemia.

Twenty-five children less than 16 years of age with acute lymphoblastic leukemia (ALL) were investigated with immunologic, cytogenetic and molecular genetic techniques at diagnosis. All pre-B-cell ALL showed clonal rearrangements in the immunoglobulin heavy chain gene (JH and/or C mu). A very high proportion of the pre-B-cell leukemias (17 of 23 cases) also showed clonal rearrangements in T-cell receptor genes (T gamma and/or T beta).

Chromosomal aberrations in human amniotic cells after intermittent exposure to fifty hertz magnetic fields.

Our recent studies have shown a significant increase in the frequency of chromosomal aberrations in human amniotic cells after exposure to a sinusoidal 50 Hz, 30 microT (rms) magnetic field. To evaluate further interactions between chromosomes and electromagnetic fields, we have analyzed the effects of intermittent exposure. Amniotic cells were exposed for 72 h to a 50 Hz, 30 microT (rms) magnetic field in a 15 s on and 15 s off fashion.

Ig-gene and T-cell receptor gene rearrangements in a secondary, mono-histiocytic malignancy.

In 1984, a 21-year-old male was diagnosed with an acute lymphoblastic leukemia of pre-B cell type. Treatment with chemotherapy, including alkylating agents and prophylactic radiotherapy to the central nervous system, induced a complete remission. In June 1990, a biopsy from a supraclavicular node revealed a malignancy of mono-histiocytic type with erythrophagocytosis.

Idiopathic hemochromatosis and chromosomal damage.

Spontaneous and radiation-induced chromosome damage in cultured lymphocytes was examined in a pilot study of 11 patients with idiopathic hemochromatosis and matched controls. Increased frequencies of chromosome breaks were found in the patients, both spontaneously and after exposure to ionizing radiation, but the differences between patients and controls were not statistically significant (p greater than 0.05) when individual data were analyzed.

Multiple DNA rearrangements in the BCL2 region in a patient with follicular lymphoma.

A 39-year-old male with follicular non-Hodgkin's lymphoma was repeatedly studied with respect to DNA rearrangements with the two probes pFL-1 and pFL-2, representing two segments of chromosome 18. The oncogene BCL2, detected by pFL-1, was as expected translocated to the J region of the immunoglobulin locus. The standard BCL2 translocation was found in three samples, one obtained at diagnosis, one ten months later, and one after 5 years.

Is the genotoxic effect of arsenic mediated by oxygen free radicals?

Previous investigations have shown that trivalent arsenic is inducing chromosomal aberrations and sister chromatid exchanges (SCEs). In a search for the genotoxic mechanism we have studied the effects of the oxygen-radical-scavenging enzymes superoxide dismutase (SOD) and catalase (CAT) on arsenic-induced SCEs in cultured human lymphocytes. The results indicate that SOD and possibly also CAT have a protective effect against arsenic-induced DNA damage.

Cytogenetic and flow cytometric DNA analysis in renal cell carcinoma.

Cytogenetic and flow cytometric DNA analyses were performed on 37 tumor samples from 16 patients with renal cell carcinoma. 36 cultures were chromosomally abnormal and 1 was normal. The most frequent abnormality was trisomy or tetrasomy of chromosome 7 (13 of 16 tumors), suggesting that this abnormality might be a primary change in renal cell carcinoma.

Cytogenetic abnormalities and leukemic transformation in hydroxyurea-treated patients with Philadelphia chromosome negative chronic myeloproliferative disease.

Eighty-one consecutive hydroxyurea-treated patients with Philadelphia (Ph) chromosome negative chronic myeloproliferative disease were followed prospectively from 1981 to 1989; 35 of them had polycythemia vera, 32 had essential thrombocythemia, 12 had myelofibrosis, and 2 had myeloproliferative syndromes. The 81 patients were treated with hydroxyurea for a total of 3,804 months during the observation time. Only three patients had been treated with alkylating agents or 32P before start of hydroxyurea treatment.

Fragility of the centromeric region of chromosome 1 associated with combined immunodeficiency in siblings. A recessively inherited entity?

Instability of the centromeric region of chromosome 1, and multibranched configurations formed by the short and long arms were seen in a brother and sister with facial dysmorphism, mental retardation and recurrent infections. No chromosomal abnormalities were seen in the parents, who were first cousins. The fragility of chromosome 1 was identified in amniotic fluid cells of the sister.

An inter-Nordic prospective study on cytogenetic endpoints and cancer risk. Nordic Study Group on the Health Risk of Chromosome Damage.

To investigate whether high rates of chromosomal aberrations (CAs), sister chromatid exchange (SCE), or micronuclei(MN) in peripheral lymphocytes indicate an increased risk for subsequent cancer, a prospective cohort study of 2,969 subjects cytogenetically examined between 1970 and 1988 in four Swedish, two Finnish, and two Norwegian laboratories was initiated. To standardize for the interlaboratory variation, the results of the three cytogenetic endpoints were trichotomized for each laboratory into "low" (1st to 33rd percentile), "medium" (34th to 66th percentile), and "high" (67th to 100th percentile]. Thirty-four cancers had been diagnosed in the cohort during the observation period (1970 to 1985).

The effect of CPH 82 on the growth of human lymphocytes in vitro. Definition of cytobiological action.

A drug composed of two semisynthetic podophylline derivatives, CPH 82, has recently been launched for the treatment of severe rheumatoid arthritis. The present in vitro study of PHA-stimulated human T-lymphocytes showed that CPH 82 arrested cell division in a metaphase-like configuration. The cell cycle effects of CPH 82 were indistinguishable from the cell cycle effects of the classical microtubule depolymerizers, Colcemid (a colchicine derivative) and podophyllotoxin.

Philadelphia chromosome negative acute lymphoblastic leukemia preceding Philadelphia positive chronic myelogenous leukemia.

A patient with Philadelphia chromosome (Ph) negative acute lymphoblastic leukemia (ALL, FAB type L1) developed Ph-positive chronic myelogenous leukemia (CML) after more than 2 years in complete remission. Subsequently, Ph-positive lymphoblastic transformation occurred, which was again successfully treated. Thereafter, the CML state was interrupted twice more by blast crisis.

t(6;9) in bone marrow cells in two patients with sarcoidosis and acute myeloid leukemia.

A t(6;9) was seen in bone marrow aspirates from two patients with sarcoidosis who developed acute myeloid leukemia. This is a new observation not previously reported.

Homozygosity for the transthyretin-met30-gene in two Swedish sibs with familial amyloidotic polyneuropathy.

Familial amyloidotic polyneuropathy (FAP) is an autosomal dominant inherited disorder. Recent biochemical studies have revealed that amyloid protein in FAP of Japanese, Swedish and Portuguese origin mainly consists of a variant transthyretin (TTR) (formerly called prealbumin) with one amino acid substitution of methionine for valine at position 30. In a 56-year-old man with typical polyneuropathy, gastrointestinal problems and vitreous amyloid, we diagnosed homozygosity for the TTR-met30-gene using RFLP analysis.

Cluster formation in PHA-stimulated mononuclear cells from peripheral blood: effects of colcemid and taxol.

Mononuclear cells from peripheral blood were incubated with phytohemagglutinin (PHA) for 24-72 hours. The cells formed dense cell clusters with firm cell-to-cell attachment and signs of cell communication, proliferation and differentiation. At the end of a 72-hour period of incubation, the test preparations were treated for 90 minutes with the classical microtubule antagonist Colcemid and the new microtubule antagonist taxol.

Chromosomes in renal carcinoma with reference to intratumor heterogeneity.

Cytogenetic studies of renal tumors from seven patients were performed (six renal cell carcinomas, one transitional cell carcinoma). Multiple samples were obtained from each tumor as well as one sample from normal tissue. Cultures were established after collagenase disaggregation.

Diagnosis of familial amyloidotic polyneuropathy in Sweden by RFLP analysis.

Genomic DNA from 17 Swedish patients with familial amyloidotic polyneuropathy (FAP), and 50 healthy controls were tested with a cDNA transthyretin probe. In seven of the patients, FAP was not reported in either of their parents. All 50 controls showed restriction fragments of 6.

Chromosomal effects in lymphocytes of 400 kV-substation workers.

In a previous study we found an increased rate of chromosomal aberrations in substation workers. To follow up this finding we in this study present data from 38 employees of electric power companies; 19 of the subjects worked with the repair and maintenance of circuit breakers and disconnectors in 400 kV-substations. The other 19 served as controls and were only exposed to normal environmental electromagnetic fields.