PURPOSE: Fragile sites are points on chromosomes which tend to break non-randomly when exposed to specific chemical agents or conditions of tissue culture. The chromosomal break induced by the antineoplastic drug, 1-beta-D-arabinofuranosyl-cytosine(Ara-c), was investigated to study the laboratory conditions in which the incidence of chromosomal break could be enhanced. Besides, the fragile sites induced by Ara-C were investigated and compared to the already known locations of the specific chromosomal alterations observed in specific neoplasms. METHODS: T-lymphocytes from theree normal males and three females were cultured for 48 hours. Cells from each individual were exposed to the Ara-C for an additional 24 hours. After the caffeine was added during the last six hours culture, the metaphase chromosomes were prepared following the conventional method. A site was considered fragile if it was found to break two or more per 100 chromosomal breaks in more than four of six individuals tested. RESULTS: Ara-C induced 252.1 chromosomal breaks per 100 mitotic cells and this result was significantly higher than that of the control, which induced 25.2 breaks(P<0.05). The incidence of the chromosomal break by Ara-C was higher, if cultured in the MEM-FA, which has no folic acid, than in the RPMI 1640 which contains enough folic acid(P<0.05). The most common break site by Ara-C was 3p14.2(FRA3B). There were 20 fragile sites induced by Ara-C. Among these 20 fragile sites, seven coincided with the locations of the mapped oncogenes, JUN, SKI, REL, N-MYC, FHIT, MET, ETS-1, and FOS. CONCLUSIONS: S phase specific chemotherapeutic agent, Ara-C, induced the expression of the chromosomal fragile sites effectively using the T-lymphocyte in vitro. Some of the fragile sites by Ara-C highly coincided with the oncogenes and neoplasm specific chromosome breakpoints. In this regard, the fragile sites reported here could provide the unknown neoplasm related chromosomal alternation points.
Caffeine ; Chromosome Breakage ; Chromosome Breakpoints ; Cytarabine ; Female ; Folic Acid ; Genes, jun ; Humans ; Incidence ; Male ; Metaphase ; Oncogenes ; S Phase ; T-Lymphocytes

Pterygium, a disease of unknown origin and pathogennesis, is a chronic condition characterized by the encroachment of triangular portion of the bulbar conjunctiva onto the cornea. We have studied the expression of extracellular matrix genes and oncogenes in cultured pterygium using Northernm dot, and slot blot hybridizations. Northern hybridization with total RNA isolated from passaged (4-8 passages) cultures demonstrated expression of genes for alpha1(I) and alpha1(III) procollagen, fibronectin, and c-Ha-ras, but no expression of gene for c-myc was observed. The pterygium exhibited significantly increased expression of alpha1(I) and alphal(III) procollagen genes when compared with normal control cells(p<0.01). And We observed there were no differences between pterygium and normal control cells in the expression of genes for fibronectin and c-Ha-ras. According to these results we thought that the causes of pterygium may be related to the increased expression of alpha1(I) and alphal(III) procollagen genes but may not be related to c-Ha-ras, c-myc, and fibronectin genes.
Conjunctiva ; Cornea ; Extracellular Matrix ; Fibroblasts ; Fibronectins ; Genes, myc ; Oncogenes ; Procollagen ; Pterygium ; RNA

Pterygium, a disease of unknown origin and pathogennesis, is a chronic condition characterized by the encroachment of triangular portion of the bulbar conjunctiva onto the cornea. We have studied the expression of extracellular matrix genes and oncogenes in cultured pterygium using Northernm dot, and slot blot hybridizations. Northern hybridization with total RNA isolated from passaged (4-8 passages) cultures demonstrated expression of genes for alpha1(I) and alpha1(III) procollagen, fibronectin, and c-Ha-ras, but no expression of gene for c-myc was observed. The pterygium exhibited significantly increased expression of alpha1(I) and alphal(III) procollagen genes when compared with normal control cells(p<0.01). And We observed there were no differences between pterygium and normal control cells in the expression of genes for fibronectin and c-Ha-ras. According to these results we thought that the causes of pterygium may be related to the increased expression of alpha1(I) and alphal(III) procollagen genes but may not be related to c-Ha-ras, c-myc, and fibronectin genes.
Conjunctiva ; Cornea ; Extracellular Matrix ; Fibroblasts ; Fibronectins ; Genes, myc ; Oncogenes ; Procollagen ; Pterygium ; RNA

OBJECTIVE: Comparative genomic hybridization was performed to evaluate DNA sequence copy number changes in human ovarian carcinomas from paraffin-embedded tissue blocks. PATIENTS AND METHODS: DNA from 20 cases of primary ovarian carcinomas underwent comparative genomic hybridization to evaluate the extent of genetic gains or losses in a test sample. RESULTS: In thirteen cases of 20 samples, varying degree of genetic imbalances was observed. Of the remaining 7 cases, two revealed normal, five failed to yield a result. Most common genetic imbalances are 8q22.2-q24 site amplification and 12p site amplification, where c-myc gene and k-ras gene respectively are included. Second most common site of genetic imbalance is 7p21-pter site deletion. CONCLUSION: Our results have shown many chromosomal alterations in human ovarian carcinomas, and these sites are known previously as oncogene or tumor-suppression gene, and some sites are not known specific cancer associated sites. Our data can be useful for screening chromosomal changes and molecular mechanism of human ovarian carcinogenesis.
Base Sequence ; Carcinogenesis ; Comparative Genomic Hybridization* ; DNA ; Genes, myc ; Genes, ras ; Humans ; Mass Screening ; Oncogenes ; Ovarian Neoplasms

The expression of the p53 protein (p53) was compared with those of several oncogenes including c-fos (Fos), c-jun (Jun), and epidermal growth factor receptor (EGFR1) using immunohistochemistry in frozen and paraffin-embedded sections of 25 basal cell carcinomas (BCCs) to find out any correlation between p53 and oncogenes in the pathogenesis of human BCC. In normal skin, positive reactions were obtained for EGFR1 and Fos, while p53 and Jun were negative in all cases. In the lesions, EGFR1 was observed in all cases and p53 was positive in 9 of 25 (36%). Fos was expressed in 21 of 25 (84%) and four negative cases were all p53-positive; this negative correlation between p53 and Fos staining was statistically significant (P< 0.01). Jun was detected in 14 of 20 (70%) and no significant relationship was observed between the expression of Jun and Fos or p53. These data suggest the possibility of down regulation of Fos expression by high levels of p53 protein. Further work is necessary to determine the mechanism of this interaction.
Aged ; Carcinoma, Basal Cell/chemistry/*genetics ; Comparative Study ; Female ; Gene Expression ; Genes, fos ; Genes, jun ; Genes, p53 ; Human ; Immunohistochemistry ; Male ; Middle Age ; Oncogene Protein p65(gag-jun)/analysis ; Oncogene Proteins v-fos/analysis ; *Oncogenes ; Protein p53/analysis ; Receptor, Epidermal Growth Factor/analysis ; Skin Neoplasms/chemistry/*genetics

The discovery of oncogenes and tumor suppressor genes have made it possible to partly understand the mechanism of cancer development. It is generally accepted that the cancer development is caused by specific gene alterations and now more than 100 oncogenes and suppressor genes are known to be involved in human carcinogenesis. However, there are only a few reports about oncogene expression on bone tumors. The author carried out an immunohistochemical study to reveal the oncogene and suppressor genes on carcinogenesis of bone tumors using antibodies against c-myc, c-H-ras, p53 and EGF. In 32 cases of osteochondrorma, EGF, p53 and c-myc antisera revealed positive reaction in 4 (12.5%), 2 (6.3%) and 7 (21.9%) cases, and, in 4 cases of chondrosarcoma, c-myc antisera revealed positive reaction in 2 (50%) cases. In 21 cases of osteosarcoma, the positive reaction of p53 was noted in 10 (47.6%) cases and that of c-myc in 3 (14.3%) cases. In 14 cases of fibrous bone tumors, there are only 2 (14.3%) cases of positive reaction with p53. These results suggest some roles of the p53 and c-myc genes in osteosarcoma development and c-myc gene in osteochondroma and chondrosarcoma development.
Antibodies ; Carcinogenesis ; Chondrosarcoma ; Epidermal Growth Factor ; Genes, myc ; Genes, Suppressor ; Genes, Tumor Suppressor* ; Humans ; Immune Sera ; Oncogene Proteins ; Oncogenes* ; Osteochondroma ; Osteosarcoma

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Oncogenes

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Oncogenes

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Oncogenes

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Oncogenes