Human cytogenetic dosimetry: a dose-response relationship for alpha particle radiation from 241Am.
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Biomedical subjects
Publications and source records attributed to L G Littlefield.
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Cytogenetic studies of 977 lymphocyte cultures from ten normal men and 54 normal women have shown: (1) variations in the frequencies of chromosome breakages among consecutive cultures from the same person and among cultures from different people, indicating that many extraneous factors may affect lymphocyte chromosomes, and (2) significantly higher average breakages in cultures from nulligravidas taking oral contraceptives (OC) and in pregnant women who had had previous pregnancies than in nulligravidas who had never taken the pill. The increase in breakages in cultures from the OC users was not observed in all cultures and could not be correlated with length of time on pill or stage of the pill cycle, suggesting that synthetic hormones do not directly damage lymphocyte chromosomes. Since estrogens and progestogens are known to affect many metabolic and biochemical systems, it is possible that these substances may induce in OC users and pregnant women a slightly altered in vivo condition in which increased chromosome breakages may be expressed.
We observed the clinical aspects and cytogenetic findings of Burkitt lymphoma in three American children. The clinical manifestations vary widely, which makes early diagnosis difficult but important.
To determine whether exposure to synthetic hormones resulted in increased chromosome damage in cells other than lymphocytes, we evaluated series of lymphocyte and fibroblast cultures from five control women and five women taking oral contraceptives (OC). The results of this study showed: (1) no difference in chromosome breakages between lymphocytes and fibroblasts; (2) no differences in breakages in replicate fibroblast cultures exposed to fetal calf serum, autologous serum, homologous serum, or homologous serum from OC users; (3) no difference in breakage between lymphocyte and fibroblast cultures from OC users, compared with lymphocyte and fibroblast cultures from control women; and (4) no increase in the frequency of cytogenetically aberrant stem-lines in fibroblast cultures from women taking OC. These findings suggest that synthetic hormones do not cause increased chromosome breakages in fibroblasts from women taking OC.
Adriamycin (AM) induced chromosome lesions and cell division delay in human foreskin fibroblasts. Cells treated with 0.01, 0.03, and 0.05 mug AM/ml culture medium for 1 hour and evaluated 5-12 hours post treatment exhibited a wide spectrum of cytogenetic injuries, ranging from moderately damaged metaphases with predominantly simple chromatid-type lesions to heavily damaged metaphases with chromosome stickiness and fragmentation. In moderately damaged metaphases that could be scored for specific types of aberrations, we observed a paucity of chromatid exchanges and chromosome-type lesions even in cultures having a very high frequency of breakages. Further, the distribution of breaks among chromosomes within groups A-G appeared to be random, which suggested that the drug does not show breakage specificity in human fibroblasts; The number of heavily damaged metaphases increased with an increase in concentration of AM and with longer periods of recovery.
During a 7 1/2-yr period we monitored a chromosomally aberrant cell line in a woman with acute granulocytic leukemia (AGL) whose disease followed a rather unusual course. Her initial remission induced with 6-mercaptopurine (6-MP) and prednisone was maintained for 52 mo with biweekly doses of methotrexate (MTX) given orally. Because signs of liver dysfunction occurred, maintenance therapy was stopped. After 15 mo without chemotherapy, she suffered her first relapse (5 yr 7 mo after the initial diagnosis). A second remission, again induced with 6-MP and prednisone, was maintained for 1 yr, after which a second relapse occurred. Another remission lasting for only 4 mo was followed by a relapse of the leukemic process which led to her death. Cytogenetic studies of marrow cells and peripheral blood at the time of her initial diagnosis showed abnormal stem lines with characteristic chromosome markers. A small percentage of malignant cells bearing these markers persisted in her marrow during the years of her prolonged remission. At the time of her first relapse, 75% of her marrow cells had the marker karyotype, and at the time of her death (7 1/2 yr after the leukemia was diagnosed) all analyzable marrow metaphases had the characteristic chromosome changes.
In a recent study of chromosome breakage frequencies in 36 primary fibroblast cell strains derived from skin from 10 phenotypically normal women, we observed seven different clones of cells having consistent chromosomal abnormalities. Five of the stem lines were noted in cultures from "control" women and two in fibroblasts from women taking oral contraceptives. We observed aneuploid clones as well as stem lines bearing structural abnormalities (e.g., translocation, inversions). The various aberrant clones were found in cultures ranging in age from 41 to 144 days and comprised varying percentages of the cell populations ranging from 0.8% to virtually 100%. The possible evolution in culture of clones of cells having aberrant karyotypes should be considered in interpreting findings from fibroblast cultures initiated for clinical evaluation.
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12-O-Tetradecanoylphorbol-13-acetate (TPA), a potent tumor promoter, can induce differentiation of human promyelocytic leukemia cells grown in a serum-free environment. Removal of serum produces altered acyl group composition of cellular phospholipids, most notably, marked decreases in the polyunsaturated fatty acid content. Although higher amounts of TPA are required to induce differentiation in serum-free cell populations, induction assessed by morphological and enzymatic markers in similar to the "macrophage-like' differentiated state reported for cells grown in a serum-rich medium.