Chromosome Abnormalities In Lymphocytes Research Articles

3p Abnormalities in Peripheral Lymphocytes in Small Cell Lung Cancer

3p abnormalities are the most frequent chromosome abnormalities in small cell lung cancer (SCLC). To date these abnormalities have only been observed in cells derived from tumor tissues. It is thought that cancer-related chromosome abnormalities in peripheral lymphocytes could help to predict cancer development, prognosis, and future metastasis. We report clonal and nonclonal 3p abnormalities in the peripheral lymphocytes of two patients with SCLC. A standard T-lymphocyte culture method and GTL banding technique were applied to the samples, and various clonal and nonclonal chromosome 3 abnormalities, i.e., -3, del(3)(p24), del(3)(p21), del(3)(p11), del(3)(q22), inv(3)(p14q29), and inv(3)(q21q29) were observed. Efforts have been made to understand if there are cancer-related chromosome abnormalities in lymphocytes and the suitability of these abnormalities to predict cancer development or metastases. As far as we know, this is the first report on chromosome 3 abnormalities in lymphocytes. Since 3p abnormalities are specific for SCLC, it is important to show that these cancer-related abnormalities can be found in blood cells.

Chromosome abnormalities in lymphocytes and fibroblasts of subjects with multiple endocrine neoplasia type 1

A consistent degree of chromosome instability was found in cultured lymphocytes and in fibroblasts derived from skin biopsies of three patients with multiple endocrine neoplasia type 1 (MEN1). In both tissues, there was a significant increase in chromosomal breakage. Dicentrics and tricentrics, rings, translocations, deletions, acentric fragments, and presumptive double minutes were the most frequent abnormalities in lymphocytes. The fibroblasts of two patients had large clones consisting of trisomy 7 and trisomy 18 cells, respectively.

Cytogenetic Analysis of Human Bile for Mutagenicity and Co-Mutagenicity.

Cytogenetic analysis was used to test whether or not human bile induced chromosome abnormalities in lymphocytes grown in culture. Bile was obtained from gallbladders resected for various reasons such as cholecystitis, cholelithiasis, polypus and cancers of the biliary tract, stomach and pancreas. After adding human bile to a final concentration of 25 microliters/ml or 12.5 microliters/ml, the culture medium was incubated at 37 degrees C for 72 hr. Air-dried slides were stained with conventional Giemsa and the numerical and structural chromosome abnormalities were scored. Positive and negative controls in terms of chromosome abnormalities were established by using 0.03 micrograms/ml mitomycin C (MMC) and 0.9% normal saline, respectively. Cytogenetic analysis was successfully performed in 6 out of 10 bile samples (60.0%). Bile alone did not induce numerical or structural chromosome abnormalities. Structural abnormalities increased significantly in the 25 microliters/ml bile + 0.03 micrograms/ml MMC group, compared with the 0.03 micrograms/ml MMC group: 36.0% vs. 20.7% in the chromatid-type gaps and breaks, 27.8% vs. 22.7% in the chromosome-type gaps and breaks, and 8.3% vs. 3.2% in the exchange-type abnormalities. It is likely that the interaction between bile and MMC is synergistic rather than additive.

The lymphocyte as a marker of past nutritional status: persistence of abnormal lymphocyte deoxyuridine (dU) suppression test and chromosomes in patients with past deficiency of folate and vitamin B12.

In short‐term suspension cultures of bone marrow cells or PHA‐stimulated lymphocytes from normal subjects, non‐radioactive deoxyuridine (dU) suppresses the incorporation of radioactive thymidine ([3H]TdR) or its analogue, [125I]deoxyuridine ([125I]Udr), into DNA. This normal suppression by deoxyuridine (dU) is impaired in both of these cell systems from patients with deficiency of folate or vitamin B12, and corrected by the appropriate vitamin. Patients with megaloblastic anaemia due to deficiency of vitamin B12 or folate were studied before and after treatment. When treatment had returned to normal the bone marrow morphology and the serum and red cell vitamin levels, then the dU suppression test and chromosomal changes in the bone marrow were also corrected. However, the dU suppression test and chromosomal changes remained abnormal in lymphocytes as long as 84 d after therapy. These abnormal lymphocyte dU suppression tests were corrected by the appropriate in vitro additions of folic acid, methylfolate and vitamin B12, depending on the vitamin deficiency present before therapy. These studies suggest that an abnormal lymphocyte dU suppression test corrected by the appropriate vitamin in vitro, and characteristic chromosome abnormalities in lymphocytes, when these are absent in the bone marrow, indicate past deficiency of vitamin B12 or folate. These changes can be used for retrospective diagnosis of these deficiencies in patients treated by ‘shotgun’ therapy. They further support the concepts that circulating unstimulated lymphocytes: (1) do not incorporate appreciable amounts of vitamin B12 or folic acid; (2) reflect the vitamin status of the patient at the time the lymphocytes were generated; and (3) cannot replace bone marrow in dU suppression tests aimed at diagnosis of current marrow and other non‐lymphocyte cell line nutrient status. These studies add to the evidence that selective nutrient deficiency may occur in one but not another cell line in the same person, and point to the need for more studies on factors affecting nutrient delivery, uptake, and utilization by various human cell lines. These studies also provide a new approach to evaluation of circulating lymphocyte age.

Chromosome abnormalities in lymphocytes from normal human subjects. A study of 3,720 cells.

The occurrence of chromosome gaps, breaks and rearrangements was determined in 3,720 lymphocyte metaphases obtained from ten normal adults. The frequency of the cells with one or more breaks varied from 1–20%, and the maximum variation found in one individual during sequential cultures was 6–20%. Multiple breaks were found in only 17 cells, and a structural rearrangement (translocation, dicentric inversion or triradial configuration) occurred in eight cells. Chromatid breaks were not randomly distributed, occurring most frequently as subterminal breaks in the long arm of No. 16 in both sexes and the short arm of the No. 3 in females. Previous studies demonstrating an increased number of breaks in these areas following treatment with a variety of agents may be best explained by an accentuation of the normally occurring pattern of breaks.