Distribution of X-Ray-induced chromosome breakpoints in Down syndrome lymphocytes
Down syndrome (DS) individuals are known to be predisposed to develop leukemia and their lymphocytes are highly sensitive to the induction of chromosome aberrations by X‐rays. A study was conducted to identify the chromosome breakpoints and to evaluate whether site specificity for chromosome breakag...
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Veröffentlicht in: | American Journal of Medical Genetics, Suppl.; (USA) Suppl.; (USA), 1990, Vol.37 (S7), p.195-200 |
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description | Down syndrome (DS) individuals are known to be predisposed to develop leukemia and their lymphocytes are highly sensitive to the induction of chromosome aberrations by X‐rays. A study was conducted to identify the chromosome breakpoints and to evaluate whether site specificity for chromosome breakage and rearrangement may exist which may explain the predisposition phenomenon. DS lymphocytes at the G1 phase of the cell cycle were irradiated with 300, 450, and 600 rad of X‐rays. Cells were harvested after 3 days in culture and 193 G‐banded karyotypes were analyzed to identify the induced chromosome abnormalities. Out of 273 breakpoints identified, 122 were involved in the formation of stable chromosome rearrangements and 151 in the formation of unstable abnormalities. The Poisson analysis of these breakpoints demonstrated that 16 chromosome bands located in chromosomes 1, 3, 7, 12, 17, 19 and X were preferentially involved in breakage and rearrangement (P < 0.05). These 16 bands are also found to be locations of “cancer breakpoints,” oncogenes, or fragile sites. Many abnormal cells were observed to carry stable chromosome rearrangements only. Therefore, these cells are presumed to be compatible with survival and to be “initiated” in the transformation process. We propose that similar stable and site‐specific chromosome rearrangements may exist in proliferating cells in DS individuals after exposure to clastogens and that this abnormality predisposes them to develop leukemia. |
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A study was conducted to identify the chromosome breakpoints and to evaluate whether site specificity for chromosome breakage and rearrangement may exist which may explain the predisposition phenomenon. DS lymphocytes at the G1 phase of the cell cycle were irradiated with 300, 450, and 600 rad of X‐rays. Cells were harvested after 3 days in culture and 193 G‐banded karyotypes were analyzed to identify the induced chromosome abnormalities. Out of 273 breakpoints identified, 122 were involved in the formation of stable chromosome rearrangements and 151 in the formation of unstable abnormalities. The Poisson analysis of these breakpoints demonstrated that 16 chromosome bands located in chromosomes 1, 3, 7, 12, 17, 19 and X were preferentially involved in breakage and rearrangement (P < 0.05). These 16 bands are also found to be locations of “cancer breakpoints,” oncogenes, or fragile sites. Many abnormal cells were observed to carry stable chromosome rearrangements only. Therefore, these cells are presumed to be compatible with survival and to be “initiated” in the transformation process. We propose that similar stable and site‐specific chromosome rearrangements may exist in proliferating cells in DS individuals after exposure to clastogens and that this abnormality predisposes them to develop leukemia.</description><identifier>ISSN: 0148-7299</identifier><identifier>ISSN: 1040-3787</identifier><identifier>EISSN: 1096-8628</identifier><identifier>DOI: 10.1002/ajmg.1320370740</identifier><identifier>PMID: 2149946</identifier><language>eng</language><publisher>New York: Wiley Subscription Services, Inc., A Wiley Company</publisher><subject>560120 - Radiation Effects on Biochemicals, Cells, & Tissue Culture ; ANIMAL CELLS ; BIOLOGICAL EFFECTS ; BIOLOGICAL MATERIALS ; BIOLOGICAL RADIATION EFFECTS ; BLOOD ; BLOOD CELLS ; BODY FLUIDS ; CELL CYCLE ; Cells, Cultured ; Chi-Square Distribution ; Child ; Child, Preschool ; CHROMOSOMAL ABERRATIONS ; Chromosome Aberrations ; Chromosome Banding ; chromosome breakpoints ; Chromosome Fragile Sites ; Chromosome Fragility ; Chromosomes, Human - radiation effects ; CONGENITAL MALFORMATIONS ; CONNECTIVE TISSUE CELLS ; DISEASES ; Down Syndrome - genetics ; Down syndrome lymphocytes ; Down's syndrome ; DOWNS SYNDROME ; ELECTROMAGNETIC RADIATION ; Female ; fragile sites ; GENES ; GENETIC EFFECTS ; GENETIC RADIATION EFFECTS ; HEMIC DISEASES ; HEREDITARY DISEASES ; Humans ; IMMUNE SYSTEM DISEASES ; Infant ; IONIZING RADIATIONS ; KARYOTYPE ; Karyotyping ; LEUKEMIA ; LEUKOCYTES ; LYMPHOCYTES ; Male ; MALFORMATIONS ; MATERIALS ; MUTATIONS ; NEOPLASMS ; ONCOGENES ; PATHOLOGICAL CHANGES ; RADIATION EFFECTS ; RADIATION, THERMAL, AND OTHER ENVIRON. 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J. Med. Genet</addtitle><description>Down syndrome (DS) individuals are known to be predisposed to develop leukemia and their lymphocytes are highly sensitive to the induction of chromosome aberrations by X‐rays. A study was conducted to identify the chromosome breakpoints and to evaluate whether site specificity for chromosome breakage and rearrangement may exist which may explain the predisposition phenomenon. DS lymphocytes at the G1 phase of the cell cycle were irradiated with 300, 450, and 600 rad of X‐rays. Cells were harvested after 3 days in culture and 193 G‐banded karyotypes were analyzed to identify the induced chromosome abnormalities. Out of 273 breakpoints identified, 122 were involved in the formation of stable chromosome rearrangements and 151 in the formation of unstable abnormalities. The Poisson analysis of these breakpoints demonstrated that 16 chromosome bands located in chromosomes 1, 3, 7, 12, 17, 19 and X were preferentially involved in breakage and rearrangement (P < 0.05). These 16 bands are also found to be locations of “cancer breakpoints,” oncogenes, or fragile sites. Many abnormal cells were observed to carry stable chromosome rearrangements only. Therefore, these cells are presumed to be compatible with survival and to be “initiated” in the transformation process. We propose that similar stable and site‐specific chromosome rearrangements may exist in proliferating cells in DS individuals after exposure to clastogens and that this abnormality predisposes them to develop leukemia.</description><subject>560120 - Radiation Effects on Biochemicals, Cells, & Tissue Culture</subject><subject>ANIMAL CELLS</subject><subject>BIOLOGICAL EFFECTS</subject><subject>BIOLOGICAL MATERIALS</subject><subject>BIOLOGICAL RADIATION EFFECTS</subject><subject>BLOOD</subject><subject>BLOOD CELLS</subject><subject>BODY FLUIDS</subject><subject>CELL CYCLE</subject><subject>Cells, Cultured</subject><subject>Chi-Square Distribution</subject><subject>Child</subject><subject>Child, Preschool</subject><subject>CHROMOSOMAL ABERRATIONS</subject><subject>Chromosome Aberrations</subject><subject>Chromosome Banding</subject><subject>chromosome breakpoints</subject><subject>Chromosome Fragile Sites</subject><subject>Chromosome Fragility</subject><subject>Chromosomes, Human - radiation effects</subject><subject>CONGENITAL MALFORMATIONS</subject><subject>CONNECTIVE TISSUE CELLS</subject><subject>DISEASES</subject><subject>Down Syndrome - genetics</subject><subject>Down syndrome lymphocytes</subject><subject>Down's syndrome</subject><subject>DOWNS SYNDROME</subject><subject>ELECTROMAGNETIC RADIATION</subject><subject>Female</subject><subject>fragile sites</subject><subject>GENES</subject><subject>GENETIC EFFECTS</subject><subject>GENETIC RADIATION EFFECTS</subject><subject>HEMIC DISEASES</subject><subject>HEREDITARY DISEASES</subject><subject>Humans</subject><subject>IMMUNE SYSTEM DISEASES</subject><subject>Infant</subject><subject>IONIZING RADIATIONS</subject><subject>KARYOTYPE</subject><subject>Karyotyping</subject><subject>LEUKEMIA</subject><subject>LEUKOCYTES</subject><subject>LYMPHOCYTES</subject><subject>Male</subject><subject>MALFORMATIONS</subject><subject>MATERIALS</subject><subject>MUTATIONS</subject><subject>NEOPLASMS</subject><subject>ONCOGENES</subject><subject>PATHOLOGICAL CHANGES</subject><subject>RADIATION EFFECTS</subject><subject>RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT</subject><subject>RADIATIONS</subject><subject>RADIOINDUCTION</subject><subject>SOMATIC CELLS</subject><subject>X RADIATION</subject><issn>0148-7299</issn><issn>1040-3787</issn><issn>1096-8628</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1990</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkUtv1DAYRS1EVYaWNSukiEV3af1-iFXVodOOCqgIKDvLcRzGbWIPdqKSf9-MMipixcqS77lncT8A3iJ4iiDEZ-a--3WKCIZEQEHhC7BAUPFScixfggVEVJYCK_UKvM75HkI0feBDcIgRVYryBbhd-twnXw29j6GITfGz_GrG0od6sK4u7CbFLubYuaJKzjxsow99LnwolvExFHkMddqF7dhtN9GOvcvH4KAxbXZv9u8R-H758dvFVXnzZXV9cX5TWoopLBVykEhmpGCI1E3NTdMIYyRRqKLcwYqRplZYUMEkobwhnBHpKuiMURUhNTkC72dvzL3X2fre2Y2NITjbaya5FJhO0MkMbVP8Pbjc685n69rWBBeHrBGTSDGFJ_BsBm2KOSfX6G3ynUmjRlDvlta7pfXfpafGu716qDpXP_P7aaf8w5w_-taN_9Pp8_Wn1T_2cm5P53F_ntsmPWguiGD67vNKX65_rO-WQmlFngBS4po8</recordid><startdate>1990</startdate><enddate>1990</enddate><creator>Shafik, Hasnaa M.</creator><creator>Au, William W.</creator><creator>Whorton Jr, Elbert B.</creator><creator>Legator, Marvin S.</creator><general>Wiley Subscription Services, Inc., A Wiley Company</general><scope>BSCLL</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T3</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>OTOTI</scope></search><sort><creationdate>1990</creationdate><title>Distribution of X-Ray-induced chromosome breakpoints in Down syndrome lymphocytes</title><author>Shafik, Hasnaa M. ; Au, William W. ; Whorton Jr, Elbert B. ; Legator, Marvin S.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4240-91e0385a87513dfd6aff7aa8391b46e0b53fd9274758346f36538eb0eaa9b33d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1990</creationdate><topic>560120 - Radiation Effects on Biochemicals, Cells, & Tissue Culture</topic><topic>ANIMAL CELLS</topic><topic>BIOLOGICAL EFFECTS</topic><topic>BIOLOGICAL MATERIALS</topic><topic>BIOLOGICAL RADIATION EFFECTS</topic><topic>BLOOD</topic><topic>BLOOD CELLS</topic><topic>BODY FLUIDS</topic><topic>CELL CYCLE</topic><topic>Cells, Cultured</topic><topic>Chi-Square Distribution</topic><topic>Child</topic><topic>Child, Preschool</topic><topic>CHROMOSOMAL ABERRATIONS</topic><topic>Chromosome Aberrations</topic><topic>Chromosome Banding</topic><topic>chromosome breakpoints</topic><topic>Chromosome Fragile Sites</topic><topic>Chromosome Fragility</topic><topic>Chromosomes, Human - radiation effects</topic><topic>CONGENITAL MALFORMATIONS</topic><topic>CONNECTIVE TISSUE CELLS</topic><topic>DISEASES</topic><topic>Down Syndrome - genetics</topic><topic>Down syndrome lymphocytes</topic><topic>Down's syndrome</topic><topic>DOWNS SYNDROME</topic><topic>ELECTROMAGNETIC RADIATION</topic><topic>Female</topic><topic>fragile sites</topic><topic>GENES</topic><topic>GENETIC EFFECTS</topic><topic>GENETIC RADIATION EFFECTS</topic><topic>HEMIC DISEASES</topic><topic>HEREDITARY DISEASES</topic><topic>Humans</topic><topic>IMMUNE SYSTEM DISEASES</topic><topic>Infant</topic><topic>IONIZING RADIATIONS</topic><topic>KARYOTYPE</topic><topic>Karyotyping</topic><topic>LEUKEMIA</topic><topic>LEUKOCYTES</topic><topic>LYMPHOCYTES</topic><topic>Male</topic><topic>MALFORMATIONS</topic><topic>MATERIALS</topic><topic>MUTATIONS</topic><topic>NEOPLASMS</topic><topic>ONCOGENES</topic><topic>PATHOLOGICAL CHANGES</topic><topic>RADIATION EFFECTS</topic><topic>RADIATION, THERMAL, AND OTHER ENVIRON. 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J. Med. Genet</addtitle><date>1990</date><risdate>1990</risdate><volume>37</volume><issue>S7</issue><spage>195</spage><epage>200</epage><pages>195-200</pages><issn>0148-7299</issn><issn>1040-3787</issn><eissn>1096-8628</eissn><abstract>Down syndrome (DS) individuals are known to be predisposed to develop leukemia and their lymphocytes are highly sensitive to the induction of chromosome aberrations by X‐rays. A study was conducted to identify the chromosome breakpoints and to evaluate whether site specificity for chromosome breakage and rearrangement may exist which may explain the predisposition phenomenon. DS lymphocytes at the G1 phase of the cell cycle were irradiated with 300, 450, and 600 rad of X‐rays. Cells were harvested after 3 days in culture and 193 G‐banded karyotypes were analyzed to identify the induced chromosome abnormalities. Out of 273 breakpoints identified, 122 were involved in the formation of stable chromosome rearrangements and 151 in the formation of unstable abnormalities. The Poisson analysis of these breakpoints demonstrated that 16 chromosome bands located in chromosomes 1, 3, 7, 12, 17, 19 and X were preferentially involved in breakage and rearrangement (P < 0.05). These 16 bands are also found to be locations of “cancer breakpoints,” oncogenes, or fragile sites. Many abnormal cells were observed to carry stable chromosome rearrangements only. Therefore, these cells are presumed to be compatible with survival and to be “initiated” in the transformation process. We propose that similar stable and site‐specific chromosome rearrangements may exist in proliferating cells in DS individuals after exposure to clastogens and that this abnormality predisposes them to develop leukemia.</abstract><cop>New York</cop><pub>Wiley Subscription Services, Inc., A Wiley Company</pub><pmid>2149946</pmid><doi>10.1002/ajmg.1320370740</doi><tpages>6</tpages></addata></record> |
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subjects | 560120 - Radiation Effects on Biochemicals, Cells, & Tissue Culture ANIMAL CELLS BIOLOGICAL EFFECTS BIOLOGICAL MATERIALS BIOLOGICAL RADIATION EFFECTS BLOOD BLOOD CELLS BODY FLUIDS CELL CYCLE Cells, Cultured Chi-Square Distribution Child Child, Preschool CHROMOSOMAL ABERRATIONS Chromosome Aberrations Chromosome Banding chromosome breakpoints Chromosome Fragile Sites Chromosome Fragility Chromosomes, Human - radiation effects CONGENITAL MALFORMATIONS CONNECTIVE TISSUE CELLS DISEASES Down Syndrome - genetics Down syndrome lymphocytes Down's syndrome DOWNS SYNDROME ELECTROMAGNETIC RADIATION Female fragile sites GENES GENETIC EFFECTS GENETIC RADIATION EFFECTS HEMIC DISEASES HEREDITARY DISEASES Humans IMMUNE SYSTEM DISEASES Infant IONIZING RADIATIONS KARYOTYPE Karyotyping LEUKEMIA LEUKOCYTES LYMPHOCYTES Male MALFORMATIONS MATERIALS MUTATIONS NEOPLASMS ONCOGENES PATHOLOGICAL CHANGES RADIATION EFFECTS RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT RADIATIONS RADIOINDUCTION SOMATIC CELLS X RADIATION |
title | Distribution of X-Ray-induced chromosome breakpoints in Down syndrome lymphocytes |
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