Localization of chromatid breaks in Fanconi's anemia,using three consecutive stains

Summary The location of 339 break points was analyzed in three patients with Fanconi's anemia, using three consecutive stains: ordinary Giemsa, Q-banding, and R-banding. Almost all the breaks seem to take place in the Q bands, using R-banding, and in the R bands, using Q-banding. A very important artifact, varying according to the method used, is thus demonstrated. In fact, the breaks take place in the interbands, between R and Q bands.The breaks were also localized in relation to sister chromatid exchanges (SCEs), seen after BUDR treatment. There is a clear excess of breaks at places of SCE (29%). This may indicate a possible correlation between breaks and SCEs.Technical assitance: Anne-Marie Fosse and Martine Lombard     

C-bands in chromosomes 1,9, and 16 of twins

Summary Thirty-two pairs of Caucasoid twins, 16 monozygotic (MZ) and 16 dizygotic (DZ) of the same sex, were studied in relation to the C-bands of chromosomes 1, 9, and 16. Concordance was not absolute among MZ, the best evaluation of the degree of genetic determination for these traits being 0.40 for chromosome 16, 0.64 for chromosome 1, and 0.73 for chromosome 9. Possible explanations for the failure to obtain 100% concordance are methodologic shortcomings, intercell variations in chromosome contraction, and unequal mitotic crossing over.     

Prevention of chromosomal breakage in Fanconi's anemia by cocultivation with normal cells

Summary The frequency of aberration in cultured lymphocytes from patients with Fanconi's anemia was significantly reduced when the cells were cocultivated with normal human lymphocytes. The results suggest that most of the chromosomal aberrations observed in cultured cells from Fanconi patients arise during cultivation and that the presence of normal cells prevents chromosomal damage by means of a hitherto unknown mechanism.     

Spectrin changes occur in erythrocytes from patients with Fanconi's anemia and their parents

Fanconi's anemia (FA) is a clinically and genetically heterogeneous disease which has been hypothesized to be defective in the detoxification of reactive oxygen species. In this work we report the results obtained by morphometric analyses on the red blood cells (RBCs) from FA patients and their parents. We found that a high rate of erythrocytes from both homozygous and heterozygous subjects was significantly altered. RBCs underwent in fact cytoskeleton-dependent modifications, in particular of spectrin molecule, leading to cell shrinking and blebbing. We hypothesize that these changes may be the result of an oxidative imbalance that probably lead to alterations of RBC plasticity- and deformation-associated functions. Moreover, our results also suggest the possibility to identify FA carriers by the existence of RBC abnormalities.     

The nature of 3 cytogenetic phenomena--delayed spiralization of regions of the metaphase chromosomes, delayed disruption of the telomeric links of chromosomes and the premature division of X-chromosome centromeres

The phenomena mentioned above in the title cannot be explained by the routine scheme: gene-protein-chromatin. These are presumably associated with the existence of a system of mitotic chromosome transformation independent of the cytoplasm.     

Congenital diserythropoietic anemia type I. Report on monozygotic twins with associated hemochromatosis and short stature

We report the first occurrence of congenital dyserythropoietic anemia type I in monozygotic twins and the seventh familial occurrence to our knowledge. Mild hemochromatosis is present in the two children but has not yet required iron chelation. Moderate growth retardation, which seems to be related to pituitary failure, is also present.     

Differential behaviour of normal,transformed and Fanconi's anemia lymphoblastoid cells to modeled microgravity

Background  

Whether microgravity might influence tumour growth and carcinogenesis is still an open issue. It is not clear also if and how normal and transformed cells are differently solicited by microgravity. The present study was designed to verify this issue.     

Effects of alkylating agents on lymphocytes from controls and from patients with Fanconi's anemia

Summary The frequency of sister chromatid exchanges (SCE) and chromosome aberrations and the dynamics of cell division in peripheral blood lymphocytes of four patients with Fanconi's anemia were studied after in vitro exposure to alkylating agents TEPA and mitomycin.SCE frequency was significantly increased even after very low doses of mutagens, while chromosome aberrations were significantly increased only after high doses (0.160 g/ml mitomycin and 10^-5 M TEPA). The responses of Fanconi's anemia cells and control cells did not differ significantly. The increased frequency of both SCE and chromosome aberrations was accompanied by gradual delay of cell division, which was most conspicuous in cells from patients with Fanconi's anemia.     

Relationship of spontaneous chromosome instability and sister chromatid exchanges in Fanconi's anemia

The frequency of spontaneous instability of lymphocyte chromosomes of the first 2 mitoses, the rate of sister chromatid exchanges (SCEs), and the proliferative kinetics of lymphocytes were studied in a 6-year-old girl with Fanconi's anemia (FA) and in 4 healthy donors. The frequencies of aberrant cells and the total number of chromosome breaks in the FA patient decreased with cell transition from the first to the second mitosis. The FA lymphocytes had a slower proliferative kinetics and the level of SCEs was higher as compared with control. The probability of chromatid deletions at the sites of SCEs localization and in the dark and light stained chromatids was unequal. 33.8% of chromatid breaks were associated with SCEs. The data point to the relationship between SCEs and spontaneous chromosome instability in AF cells.     

Iron stocks and risk of anemia in twins

This study aims to compare the risk of anemia by iron deficiency in mothers and infants of twin and single pregnancy. It concerned 33 couples of twins and 31 control, all 97 being term newborns. At birth, ferritinemia is significantly lower in twins, and reticulocytes count is significantly higher; their mothers have a significantly lower hemoglobin level and higher reticulocytes percentage and count. At 3 and 6 months, hemoglobin level and mean corpuscular hemoglobin are significantly lower in twins, as at 6 months ferritinemia is significantly lower in twins. Iron stocks constituted in utero are significantly lower in twin pregnancy, and this study support the early preventive iron treatment in twins.     

Defective DNA endonuclease activities in Fanconi's anemia cells, complementation groups A and B.

Cells from patients with the inherited disorder, Fanconi's anemia (FA), were analyzed for endonucleases which recognize DNA interstrand cross-links and monoadducts produced by psoralen plus UVA irradiation. Two chromatin-associated DNA endonuclease activities, defective in their ability to incise DNA-containing adducts produced by psoralen plus UVA light, have been identified and isolated in nuclei of FA cells. In FA complementation group A (FA-A) cells, one endonuclease activity, pI 4.6, which recognizes psoralen intercalation and interstrand cross-links, has 25% of the activity of the normal human endonuclease, pI 4.6, on 8-methoxypsoralen (8-MOP) plus UVA-damaged DNA. In FA complementation group B (FA-B) cells, a second endonuclease activity, pI 7.6, which recognizes psoralen monoadducts, has 50% and 55% of the activity, respectively, of the corresponding normal endonuclease on 8-MOP or angelicin plus UVA-damaged DNA. Kinetic analysis reveals that both the FA-A endonuclease activity, pI 4.6, and the FA-B endonuclease activity, pI 7.6, have decreased affinity for psoralen plus UVA-damaged DNA. Both the normal and FA endonucleases showed approximately a 2.5-fold increase in activity on psoralen plus UVA-damaged reconstituted nucleosomal DNA compared to damaged non-nucleosomal DNA, indicating that interaction of these FA endonucleases with nucleosomal DNA is not impaired. These deficiencies in two nuclear DNA endonuclease activities from FA-A and FA-B cells correlate with decreased levels of unscheduled DNA synthesis (UDS), in response to 8-MOP or angelicin plus UVA irradiation, in these cells in culture.     

Fanconi's anemia lymphocytes: effect of caffeine, adenosine and niacinamide during G2 prophase

In this investigation peripheral blood lymphocytes from 3 Fanconi's anemia (FA) patients, 2 FA heterozygotes and 4 normal subjects were treated with caffeine and/or adenosine, and/or niacinamide during G2 prophase. Caffeine dramatically increased breakage levels in homozygote and heterozygote cells. Niacinamide and adenosine decreased the amount of chromosomal aberrations detected in FA homozygote and heterozygote lymphocytes treated and untreated with caffeine during G2 prophase. Caffeine sensitivity of heterozygote lymphocytes is proposed as a new clinical test to explore heterozygosis in individuals of FA families.     

Frequency and distribution of sister-chromatid exchanges in a case of Fanconi's anemia.

In lymphocytes of a 7-year-old boy with Fanconi's anemia the frequencies and sites of sister-chromatid exchanges (SCE) were studied with the BrdU-Giemsa method. The average frequency of SCE (8.8 per metaphase) and the inter- and intrachromosomal distribution of SCE was not significantly different from the controls.