In Vitro Chromosomal Radiosensitivity in Patients and in Carriers with Abnormal non-Down's Syndrome Karyotypes

Abstract

ExtractThis paper reports in vitro tests of chromosomal radiosensitivity in five children and three adults with normal karyotypes as control subjects, in seven patients (children) with chromosomal abnormalities, and in six translocation carriers (adults). Peripheral blood samples from each individual and skin fibroblast cultures from four children in the control group, five patients with chromosomal abnormalities, and one translocation carrier were irradiated with 10 and 100 rads. Nonirradiated duplicate cultures were used as controls. Blood cultures were harvested after 52 hr of incubation and fibroblast cultures were harvested 24 hr after irradiation. The frequency of chromosomal breakage caused by irradiation was calculated by subtracting the values for nonirradiated samples from those for irradiated samples. In normal control subjects, the number of chromosome-type breaks per cell per rad was 0.0024 ± 0.0009 and 0.0020 ± 0.0009 in lymphocytes of children and adults, respectively, and 0.0049 ± 0.0021 in fibroblasts of children. The number of breaks per cell per rad was 0.0055 ± 0.0017 in lymphocytes and 0.00:82 ± 0.0013 in fibroblasts of patients, and 0.0040 ± 0.0018 in lymphocytes and 0.0063 ± 0.0017 in fibroblasts of carriers. In comparison with age-matched controls, significantly elevated frequencies of breaks per cell per rad were observed in cultured lymphocytes and fibroblasts of patients, and in cultured lymphocytes of translocation carriers (Table II). After irradiation with 100 rads, the number of dicentrics and rings per cell was significantly greater in both patients and carriers of chromosomal abnormalities than in control subjects (Tables I and III). Therefore, chromosomes of cells of patients with chromosomal abnormalities and of translocation carriers were significantly more radiosensitive in vitro than those of control subjects. SpeculationPatients with chromosomal abnormalities and carriers with a translocated chromosome show greater chromosomal changes after irradiation in all age groups than do normal control subjects. These individuals, therefore, should be subjected to as little x-ray examination as possible. 514Abnormal karyotypes and chromosomal radiosensitivity 515

Cytogenetic Observations in Cultured Lymphocytes from Patients with Down's Syndrome and Measles

“…Chromosomes of cells from Down's syndrome were reported to be significantly more radiosensitive than those of control subjects [5,15]. Furthermore, patients with Fanconi's anemia, Bloom's syndrome, and ataxiatelangiectasia, who have an increased risk of malignant diseases as in Down's syndrome, were reported also to be significantly more radiosensitive than control subjects [5,6].…”

“…Furthermore, patients with Fanconi's anemia, Bloom's syndrome, and ataxiatelangiectasia, who have an increased risk of malignant diseases as in Down's syndrome, were reported also to be significantly more radiosensitive than control subjects [5,6]. We are planning to study effects of measles virus on the chromosomes of normal and Down's cells in vitro.…”

Clonal origin of Ph1-positive cells in a case of 46,XX/47,XXX/48,XXXX mosaicism associated with chronic myelocytic leukemia.

“…It has been reported that individuals with certain constitutional chromosome abnormalities, such as Down syndrome, are associated with a high risk of malignant diseases including leukemia (Sandberg 1980), and that somatic cells of such patients are hypersensitive in terms of the yield of chromosome aberrations or sister chromatid exchanges induced by radiation (Sasaki et al 1970;Higurashi and Conen 1972;Countryman et al 1977;Crossen and Morgan 1980;Preston 1981), viruses (Higurashi et a1.1973), andchemicals (O'Brien et al 1971;Kaina et al 1977;Sugimoto et al 1982). Although the unique occurrence of Ph1 in the XXX cells of our patient might be related to a certain genetic predisposition of such aneuploid cells, Ph1-positive leukemic cells in other cases of sex-chromosome mosaic have been reported to occur in chromosomally normal as well as abnormal cells, irrespective of the proportion of cell lines involved in a given mosaicism as mentioned before.…”

Chromosome Damage in Down's Syndrome Induced by Chickenpox Infection

“…l t is interesting to note that studied, and, when this was impossible, a minimum of 50 suitable cells from children with D~~~'~ syndrome have a high metaphases was examined per culture. All metaphases were exsensitivity to various mutagens such as radiation (5,12) or amined by light microscopy and records were kept of the microtransformation by S V 40 virus (16). T o gain further insight into the scope Stage position for the cell, the chromosome count, and the relationship between the diseases with high risk of malignancy and aberrations present.…”