Gamma ray-induced cancer; Ionizing radiationinduced cancer; Radiation-induced neoplastic transfor... more Gamma ray-induced cancer; Ionizing radiationinduced cancer; Radiation-induced neoplastic transformation; X-ray-induced cancer Definition Radiation ▶ carcinogenesis is a biological phenomenon whereby living normal cells are damaged by ionizing radiations which starts a progressive process causing the surviving cells to change their phenotype such that normal controls of cell death and apoptosis are lost and uncontrolled cancerous growth is initiated. Characteristics Radiation Radiation is the deposition of energy into mass. Energy can appear as both corpuscles or electromagnetic quanta or photons. Some of the elementary forms are protons, neutrons, electrons, X-rays, and gamma rays. X-rays originate outside of the nucleus of an atom while gamma rays originate within the atomic nucleus. Both are identical electromagnetic radiation with varying energies. The equivalence of matter expressed as energy is given by Albert Einstein's relation: E = mc 2 where E is energy, m is mass, and c is the velocity of light (3 Â 10 8 m/s). People are exposed to radiation naturally from the surrounding environment, from space radiation arriving on Earth, and from man-made causes such as chest and dental X-rays and fallout from nuclear weapon testing. Due to the nature of radiations, that is, they cannot be seen or smelled,
ras proto-oncogenes have traditionally been associated with the regulation and promotion of cell ... more ras proto-oncogenes have traditionally been associated with the regulation and promotion of cell growth. We have induced thymic lymphomas in N-ras(-/-) mice and in transgenic mice that overexpress wild-type N-ras and found that the lack of wild-type N-ras alleles favors the development of thymic lymphomas,whereas overexpression of wild-type N-ras protects against thymic lymphomagenesis in the presence or absence of its oncogene. To investigate the inhibitory role of wild-type N-ras in in vitro transformation, we introduced wild-type N-ras in N-ras-deficient tumor cells that lack ras activating mutations and found decreased growth in both low serum and soft agar. Taken together, our results indicate that wild-type N-ras has "tumor suppressor" activity, even in the absence of its oncogenic allele.
One of the main advantages of proposed by P. Raimondi "Crab Waist" collision scheme [1] is a stro... more One of the main advantages of proposed by P. Raimondi "Crab Waist" collision scheme [1] is a strong suppression of betatron resonances excited by beam-beam interaction. Some qualitative explanations with numerical examples, describing beam-beam resonances for different collision schemes, were given in [2]. This paper can be considered as an "appendix" (additional illustration) to that one. We performed a number of full 2D betatron tune scans (beam-beam simulations) for different collision schemes, so one can easily see how the beam-beam resonances appear and disappear, depending on the colliding conditions.
A fast and reliable method for the PCR characterization of DNA from mouse toes is described. The ... more A fast and reliable method for the PCR characterization of DNA from mouse toes is described. The toes biopsied to tag the mice are incubated for 2 h in proteinase K and heated for 15 min at 95°C. This DNA solution is directly used as a template for PCR amplification. The same procedure can be used for PCR analysis of DNA from other tissues in adult mice, mouse embryos and cultured cells. Because of minimal tissue manipulation, high-quality and high-molecular-weight DNA (fragments larger than 100–200 kb) is isolated. This procedure is performed in a single tube and requires no organic solvent extraction or centrifugation, allowing the isolation of high-molecular-weight DNA suitable for PCR amplification in a fast and reproducible way. Only the tissue excised during mice tagging is used and a large number of animals can be quickly and simultaneously analyzed as required to maintain a transgenic mice colony. In addition, this rapid and efficient procedure represents an alternative to o...
Expression of the N-ras oncogene under the control of the glucocorticoid-responsive promoter in t... more Expression of the N-ras oncogene under the control of the glucocorticoid-responsive promoter in the pheochromocytoma cell line UR61, a subline of PC-12 cells, has been used to investigate the differentiation process to neuronal cells triggered by ras oncogenes (I. Guerrero, A. Pellicer, and D. E. Burstein, Biochem. Biophys. Res. Commun. 150:1185-1192, 1988). Using ras-inducible cell lines, we observed that expression of the oncogenic N-ras p21 protein interferes with the ability of phorbol esters to induce downregulation of protein kinase C. This effect was associated with the appearance of immunologically detectable protein kinase C as well as the activity of the enzyme as analyzed either by binding of [3H]phorbol-12,13-dibutyrate in intact cells or by in vitro kinase activity. These results indicate a relationship between ras p21 and protein kinase C in neuronal differentiation in this model system. Comparison to the murine fibroblast system suggests that this relationship may be ...
Neutron radiation is known to produce tumors in animals and cause cell transformation. We have de... more Neutron radiation is known to produce tumors in animals and cause cell transformation. We have developed a protocol to efficiently induce thymic lymphomas in RF/J mice by a single acute dose of neutron irradiation. Activated ras genes were detected in 17% (4 of 24) of the tumors analyzed. One of the tumors contained a K-ras gene activated by a point mutation in codon 146. Activating ras mutations at position 146 have not been previously detected in any known human or animal tumors. The spectrum of ras mutations detected in neutron radiation-induced thymic lymphomas was different from that seen in thymic lymphomas induced by gamma radiation in the same strain of mice. These results may have important implications for the mechanisms by which different types of radiation damage DNA.
Chromosomal changes such as aneuploidies, translocations, and gene amplification occur in many mu... more Chromosomal changes such as aneuploidies, translocations, and gene amplification occur in many murine tumors. In this study, we have analyzed the changes in chromosomes at different stages of tumor development in C57BL/6J mice treated with gamma-irradiation or the chemical carcinogen, N-methylnitrosourea. Trisomy 15 occurred in both groups of mice regardless of inducing agent. The frequency of this event differed significantly in radiation-treated animals between stage I and stage II of the disease. A specific marker chromosome occurred only in the gamma-irradiated mice and not in the mice treated with N-methylnitrosourea. This marker consists of a translocation between chromosomes 1 and 5. It occurred in 43% of the gamma-irradiated animals at stage 1 of the disease and did not vary markedly during tumor development. In contrast, trisomy 15 increased in frequency between stages I and II of the disease in the same animals. These results suggest that the translocation event may be an early event in tumor development, whereas trisomy 15 may contribute to tumor progression.
The presence of point mutations in the K-ras gene was examined in murine thymic lymphomas induced... more The presence of point mutations in the K-ras gene was examined in murine thymic lymphomas induced by a single dose of N-methylnitrosourea by the RNase A mismatch cleavage method and by allelic-specific oligonucleotide hybridization of in vitro amplified DNA by polymerase chain reaction. The results show that the frequency of mutations is lower than that of tumors induced by multiple N-methylnitrosourea treatments. Four mutations identified were the aspartic acid at codon 12, a G:C to A:T transition in its second position. A G:C to T:A transversion in codon 146 was also found in one thymic lymphoma, changing the amino acid alanine to serine. The use of the RNase A assay allowed an estimation of the relative expression levels of both normal and mutant K-ras alleles. The results show that in approximately one half of the tumors the mutant allele is predominantly expressed, suggesting that the normal allele has been lost or that the mutant allele has been amplified relative to the norma...
We review experimental models of carcinogenesis in which the role of ras activation has been most... more We review experimental models of carcinogenesis in which the role of ras activation has been most thoroughly studied: skin, thymus, mammary gland and liver. Qualitative changes (point mutations), as well as quantitative changes (over-expression, increased gene dosage) contribute to the transforming phenotype induced by ras genes. The activation of the three different ras family members is associated with particular tumor types, carcinogenic agents, and carcinogenic stages, suggesting the ras proteins may be involved in different biological functions. Depending on the system, ras activation has been shown to be an early and/or a late event in the multi-step process of carcinogenesis. These data underscore the possible relationship between ras activation and cell type specificity, proliferation, differentiation or cell-cell interaction.
La Genetica Molecular En El Diagnostico De Las Patologias Humanas Estrategias Y Tecnologias Curso De Verano a Coruna 10 Al 14 De Julio De 1995 1996 Isbn 84 88301 48 0 Pags 165 171, 1996
We have produced transgenic mice that carry a foreign gene construct consisting of the N-ras prot... more We have produced transgenic mice that carry a foreign gene construct consisting of the N-ras proto-oncogene driven by the mouse mammary tumor virus (MMTV) long terminal repeat. Overexpression of the normal N-ras gene is associated with development of hyperplasias and tumors in a variety of tissues. The tumors are clearly malignant, as evidenced by the presence of metastatic lesions. Extensive analysis of the foreign ras gene in these tumors by use of polymerase chain reaction and sequencing demonstrates in all cases the absence of somatically acquired mutations at those codons normally associated with activation of the ras genes. Thus, these tumors develop from overexpression of the proto-oncogene rather than the presence of the mutated oncogene. These data demonstrate that overexpression of a protooncogene of the ras family can predispose cells in vivo to fully malignant behavior.
Gamma ray-induced cancer; Ionizing radiationinduced cancer; Radiation-induced neoplastic transfor... more Gamma ray-induced cancer; Ionizing radiationinduced cancer; Radiation-induced neoplastic transformation; X-ray-induced cancer Definition Radiation ▶ carcinogenesis is a biological phenomenon whereby living normal cells are damaged by ionizing radiations which starts a progressive process causing the surviving cells to change their phenotype such that normal controls of cell death and apoptosis are lost and uncontrolled cancerous growth is initiated. Characteristics Radiation Radiation is the deposition of energy into mass. Energy can appear as both corpuscles or electromagnetic quanta or photons. Some of the elementary forms are protons, neutrons, electrons, X-rays, and gamma rays. X-rays originate outside of the nucleus of an atom while gamma rays originate within the atomic nucleus. Both are identical electromagnetic radiation with varying energies. The equivalence of matter expressed as energy is given by Albert Einstein's relation: E = mc 2 where E is energy, m is mass, and c is the velocity of light (3 Â 10 8 m/s). People are exposed to radiation naturally from the surrounding environment, from space radiation arriving on Earth, and from man-made causes such as chest and dental X-rays and fallout from nuclear weapon testing. Due to the nature of radiations, that is, they cannot be seen or smelled,
ras proto-oncogenes have traditionally been associated with the regulation and promotion of cell ... more ras proto-oncogenes have traditionally been associated with the regulation and promotion of cell growth. We have induced thymic lymphomas in N-ras(-/-) mice and in transgenic mice that overexpress wild-type N-ras and found that the lack of wild-type N-ras alleles favors the development of thymic lymphomas,whereas overexpression of wild-type N-ras protects against thymic lymphomagenesis in the presence or absence of its oncogene. To investigate the inhibitory role of wild-type N-ras in in vitro transformation, we introduced wild-type N-ras in N-ras-deficient tumor cells that lack ras activating mutations and found decreased growth in both low serum and soft agar. Taken together, our results indicate that wild-type N-ras has "tumor suppressor" activity, even in the absence of its oncogenic allele.
One of the main advantages of proposed by P. Raimondi "Crab Waist" collision scheme [1] is a stro... more One of the main advantages of proposed by P. Raimondi "Crab Waist" collision scheme [1] is a strong suppression of betatron resonances excited by beam-beam interaction. Some qualitative explanations with numerical examples, describing beam-beam resonances for different collision schemes, were given in [2]. This paper can be considered as an "appendix" (additional illustration) to that one. We performed a number of full 2D betatron tune scans (beam-beam simulations) for different collision schemes, so one can easily see how the beam-beam resonances appear and disappear, depending on the colliding conditions.
A fast and reliable method for the PCR characterization of DNA from mouse toes is described. The ... more A fast and reliable method for the PCR characterization of DNA from mouse toes is described. The toes biopsied to tag the mice are incubated for 2 h in proteinase K and heated for 15 min at 95°C. This DNA solution is directly used as a template for PCR amplification. The same procedure can be used for PCR analysis of DNA from other tissues in adult mice, mouse embryos and cultured cells. Because of minimal tissue manipulation, high-quality and high-molecular-weight DNA (fragments larger than 100–200 kb) is isolated. This procedure is performed in a single tube and requires no organic solvent extraction or centrifugation, allowing the isolation of high-molecular-weight DNA suitable for PCR amplification in a fast and reproducible way. Only the tissue excised during mice tagging is used and a large number of animals can be quickly and simultaneously analyzed as required to maintain a transgenic mice colony. In addition, this rapid and efficient procedure represents an alternative to o...
Expression of the N-ras oncogene under the control of the glucocorticoid-responsive promoter in t... more Expression of the N-ras oncogene under the control of the glucocorticoid-responsive promoter in the pheochromocytoma cell line UR61, a subline of PC-12 cells, has been used to investigate the differentiation process to neuronal cells triggered by ras oncogenes (I. Guerrero, A. Pellicer, and D. E. Burstein, Biochem. Biophys. Res. Commun. 150:1185-1192, 1988). Using ras-inducible cell lines, we observed that expression of the oncogenic N-ras p21 protein interferes with the ability of phorbol esters to induce downregulation of protein kinase C. This effect was associated with the appearance of immunologically detectable protein kinase C as well as the activity of the enzyme as analyzed either by binding of [3H]phorbol-12,13-dibutyrate in intact cells or by in vitro kinase activity. These results indicate a relationship between ras p21 and protein kinase C in neuronal differentiation in this model system. Comparison to the murine fibroblast system suggests that this relationship may be ...
Neutron radiation is known to produce tumors in animals and cause cell transformation. We have de... more Neutron radiation is known to produce tumors in animals and cause cell transformation. We have developed a protocol to efficiently induce thymic lymphomas in RF/J mice by a single acute dose of neutron irradiation. Activated ras genes were detected in 17% (4 of 24) of the tumors analyzed. One of the tumors contained a K-ras gene activated by a point mutation in codon 146. Activating ras mutations at position 146 have not been previously detected in any known human or animal tumors. The spectrum of ras mutations detected in neutron radiation-induced thymic lymphomas was different from that seen in thymic lymphomas induced by gamma radiation in the same strain of mice. These results may have important implications for the mechanisms by which different types of radiation damage DNA.
Chromosomal changes such as aneuploidies, translocations, and gene amplification occur in many mu... more Chromosomal changes such as aneuploidies, translocations, and gene amplification occur in many murine tumors. In this study, we have analyzed the changes in chromosomes at different stages of tumor development in C57BL/6J mice treated with gamma-irradiation or the chemical carcinogen, N-methylnitrosourea. Trisomy 15 occurred in both groups of mice regardless of inducing agent. The frequency of this event differed significantly in radiation-treated animals between stage I and stage II of the disease. A specific marker chromosome occurred only in the gamma-irradiated mice and not in the mice treated with N-methylnitrosourea. This marker consists of a translocation between chromosomes 1 and 5. It occurred in 43% of the gamma-irradiated animals at stage 1 of the disease and did not vary markedly during tumor development. In contrast, trisomy 15 increased in frequency between stages I and II of the disease in the same animals. These results suggest that the translocation event may be an early event in tumor development, whereas trisomy 15 may contribute to tumor progression.
The presence of point mutations in the K-ras gene was examined in murine thymic lymphomas induced... more The presence of point mutations in the K-ras gene was examined in murine thymic lymphomas induced by a single dose of N-methylnitrosourea by the RNase A mismatch cleavage method and by allelic-specific oligonucleotide hybridization of in vitro amplified DNA by polymerase chain reaction. The results show that the frequency of mutations is lower than that of tumors induced by multiple N-methylnitrosourea treatments. Four mutations identified were the aspartic acid at codon 12, a G:C to A:T transition in its second position. A G:C to T:A transversion in codon 146 was also found in one thymic lymphoma, changing the amino acid alanine to serine. The use of the RNase A assay allowed an estimation of the relative expression levels of both normal and mutant K-ras alleles. The results show that in approximately one half of the tumors the mutant allele is predominantly expressed, suggesting that the normal allele has been lost or that the mutant allele has been amplified relative to the norma...
We review experimental models of carcinogenesis in which the role of ras activation has been most... more We review experimental models of carcinogenesis in which the role of ras activation has been most thoroughly studied: skin, thymus, mammary gland and liver. Qualitative changes (point mutations), as well as quantitative changes (over-expression, increased gene dosage) contribute to the transforming phenotype induced by ras genes. The activation of the three different ras family members is associated with particular tumor types, carcinogenic agents, and carcinogenic stages, suggesting the ras proteins may be involved in different biological functions. Depending on the system, ras activation has been shown to be an early and/or a late event in the multi-step process of carcinogenesis. These data underscore the possible relationship between ras activation and cell type specificity, proliferation, differentiation or cell-cell interaction.
La Genetica Molecular En El Diagnostico De Las Patologias Humanas Estrategias Y Tecnologias Curso De Verano a Coruna 10 Al 14 De Julio De 1995 1996 Isbn 84 88301 48 0 Pags 165 171, 1996
We have produced transgenic mice that carry a foreign gene construct consisting of the N-ras prot... more We have produced transgenic mice that carry a foreign gene construct consisting of the N-ras proto-oncogene driven by the mouse mammary tumor virus (MMTV) long terminal repeat. Overexpression of the normal N-ras gene is associated with development of hyperplasias and tumors in a variety of tissues. The tumors are clearly malignant, as evidenced by the presence of metastatic lesions. Extensive analysis of the foreign ras gene in these tumors by use of polymerase chain reaction and sequencing demonstrates in all cases the absence of somatically acquired mutations at those codons normally associated with activation of the ras genes. Thus, these tumors develop from overexpression of the proto-oncogene rather than the presence of the mutated oncogene. These data demonstrate that overexpression of a protooncogene of the ras family can predispose cells in vivo to fully malignant behavior.
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Papers by Angel Pellicer