Radiation Response of Mouse Lymphoid and Myeloid Cell Lines. Part I. Sensitivity to Killing by Ionizing Radiation, Rate of Loss of Viability, and Cell Type of Origin

Radford, Ian R.

doi:10.1080/09553009414550241

Cited by 45 publications

(23 citation statements)

References 34 publications

(25 reference statements)

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“…Di Leonardo, unpubl.). This is consistent with other studies showing that DNA-damaging agents induce apoptosis in most cells of hematopoietic lineage containing wtp53 (Walker et al 1991;Clarke et al 1993;Levy et al 1993;Lotem and Sachs 1993;Lowe et al 1993b;O'Connor et al 1993;Ryan et al 1993;YonishRouach et al 1993;Radford 1994;, as does overexpression of wtp53 (Yonish-Rouach et al 1991). It has also been shown that wtp53 plays an essential role in the radia tion-induced apoptosis of murine intestinal epithelial stem cells (Merritt et al 1994).…”

Section: Lin Et Al 1992) the Timing Of The Arrest Suggests That Thesupporting

confidence: 80%

DNA damage triggers a prolonged p53-dependent G1 arrest and long-term induction of Cip1 in normal human fibroblasts.

Leonardo¹,

Linke²,

Clarkin³

et al. 1994

Genes Dev.

1,067

639

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The tumor suppressor p53 is a cell cycle checkpoint protein that contributes to the preservation of genetic stability by mediating either a G^ arrest or apoptosis in response to DNA damage. Recent reports suggest that p53 causes growth arrest through transcriptional activation of the cyclin-dependent kinase (Cdk)-inhibitor Cipl. Here, we characterize the p53-dependent Gj arrest in several normal human diploid fibroblast (NDF) strains and p53-deficient cell lines treated with 0.1-6 Gy gamma radiation. DNA damage and cell cycle progression analyses showed that NDF entered a prolonged arrest state resembling senescence, even at low doses of radiation. This contrasts with the view that p53 ensures genetic stability by inducing a transient arrest to enable repair of DNA damage, as reported for some myeloid leukemia lines. Gamma radiation administered in early to mid-, but not late, G^ induced the arrest, suggesting that the p53 checkpoint is only active in Gj until cells commit to enter S phase at the Gi restriction point. A log-linear plot of the fraction of irradiated GQ cells able to enter S phase as a function of dose is consistent with single-hit kinetics. Cytogenetic analyses combined with radiation dosage data indicate that only one or a small number of unrepaired DNA breaks may be sufficient to cause arrest. The arrest also correlated with long-term elevations of p53 protein, Cipl mRNA, and Cipl protein. We propose that p53 helps maintain genetic stability in NDF by mediating a permanent cell cycle arrest through long-term induction of Cipl when low amounts of unrepaired DNA damage are present in G^ before the restriction point.

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Section: Lin Et Al 1992) the Timing Of The Arrest Suggests That Thesupporting

confidence: 80%

DNA damage triggers a prolonged p53-dependent G1 arrest and long-term induction of Cip1 in normal human fibroblasts.

Leonardo¹,

Linke²,

Clarkin³

et al. 1994

Genes Dev.

1,067

639

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“…This result contrasts with previous data from mouse lymphoid lines, which revealed a correlation between rate of radiation-induced apoptotic death and radiosensitiity (Radford, 1994a). However, it should be noted that, even in the RBM7 line, apoptosis is induced considerably more slowly in irradiated fibroblasts than in the more radiosensitive lymphoid lines.…”

Section: All Cell Lines Used Show Apoptotic Death Following Irradiationcontrasting

confidence: 56%

“…However, it should be noted that, even in the RBM7 line, apoptosis is induced considerably more slowly in irradiated fibroblasts than in the more radiosensitive lymphoid lines. For example, apoptotic cells were not det in RBM7 cultures until at least 8 h after irradiation (data not shown), as compared with 1-2 h in radiosensitive lymphoid ines (Radford, 1994a). The comparatively lengthy time period available to irradiated RBM7 cells, prior to possible induction of apoptosis, may be adequate for DNA repair.…”

Section: All Cell Lines Used Show Apoptotic Death Following Irradiationmentioning

confidence: 99%

“…Using a panel of mouse lymphoid or myeloid cell lines, all of which underwent apoptosis after irradiation, a correlation between the rapidity of induction of apoptosis and the clonogenic survival dose-response of a particular cell line was shown (Radford, 1994a). The greater sensitivity of these haemopoietic lines to radiation-induced DNA double-strand breaks as compared with fibroblast lines such as V79, which die by necrosis, suggested that radiosensitivity may be related to the mode of death (Radford, 1991(Radford, , 1994a. Similarly, in vivo studies with transplantable murine tumours showed that elevation of both spontaneous and radiationinduced apoptosis correlated positively with growth delay and negatively with TCD50 (dose to cure 50% of animals) (Meyn et al, 1993).…”

mentioning

confidence: 99%

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Increasing the susceptibility of the rat 208F fibroblast cell line to radiation-induced apoptosis does not alter its clonogenic survival dose-response

Aldridge

Arends²,

Radford³

1995

Br J Cancer

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Recent studies have suggested a correlation between the rate and incidence of apoptosis and the radiation response of particular cell lines. However, we found that increasing the rate of induction of apoptosis in the fibroblast line 208F, by transfecting it with human c-myc, did not lead to a change in its clonogenic survival dose-response for either '-?irradiation or "5I-induced DNA damage. It was also found that expression of mutant (T24) Ha-ras in the 208F line appeared to decrease the level of apoptosis per mitosis after irradiation and inhibited the formation of nucleosomal ladders, but did not affect either the onset of the morphological features of apoptosis or the clonogenic survival dose-response of the cells to either '--irradiation or "5I-induced DNA damage. Our findings suggest that it may be incorrect to make predictions about the radiosensitivity of cells based only on knowledge of their mode of death.

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“…A exposição à radiação ionizante induz diversas alterações nos sistemas biológicos, atingindo as várias macromoléculas biológicas, que apresentam diferentes impactos em cada tipo de célula atingida (RADFORD, 1994). Em animais unicelulares, o efeito é facilmente identificável, mas num organismo animal com múltiplos grupos celulares, a sobrevida depende de conservação das populações celulares mais radio-sensíveis após a exposição a uma fonte radioativa (UNSCEAR, 1993).…”

Section: Introductionunclassified

Avaliação dos efeitos da inibição de cadeias inflamatórias e da suplementação exógena de CXCL12 na hematopoiese de modelos experimentais expostos a doses letais ou subletais de radiação gama

Vieira¹

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AGRADECIMENTOS ESPECIAISAos meus pais, Heitor e Elizabeth, por sempre terem se dedicado de todas as formas possíveis para que este trabalho fosse realizado, porque sabiam da importância dele para mim e acreditaram, por vezes mais do que eu, que ele era possível. Muito obrigado, pai e mãe. Graças a vocês eu posso escrever estas linhas neste momento.Ao Heitor, por ter me ensinado, mesmo com a minha resistência e teimosia, o que é fazer ciência de verdade. Espero um dia ter ao menos uma parte de sua sabedoria.À D. Fran, que sempre foi um exemplo de perseverança e vontade. Espero um dia ter ao menos uma parcela da sua coragem.Ao Luciano, por ter me ensinado o que é trabalhar com seriedade. Espero um dia ter ao menos um pouco de sua força.Ao Andrés, que me acompanha desde a faculdade e por quase todas as disciplinas da pós-graduação, e sempre me ajudou em tudo que precisei, além de ter ensinado que devemos ter confiança no próprio trabalho.Ao Franco, por ter proporcionado a descontração necessária à manutenção da seriedade, e a ter me ensinado a não me importar com qualquer pequenez que encontramos na vida.Aos meus amigos de longa data, Carlos, Antônio, Marcus e Gisele, que me ajudaram muito a manter a sanidade durante a redação deste trabalho. Espero um dia poder retribuir na mesma medida. A todos os funcionários e estudantes do Centro de Biologia Molecular/IPEN pela recepção sempre simpática e amigável que sempre recebi. AGRADECIMENTOSA todos os funcionários e estudantes do Laboratório de Virologia do Instituto de Medicina Tropical de São Paulo, pela compreensão ao ceder a estrutura do seu laboratório, ajuda sem a qual este trabalho não estaria terminado.À Comissão de Pós-Graduação do IPEN pelo auxílio sempre prestado.Ao CNPq pelo apoio financeiro.Ao LIMHCFMUSP49 e à Divisão de Radiobiologia / IPEN pelo suporte ao trabalho. SE Rudyard KiplingSe és capaz de manter tua calma, quando todo mundo ao redor já a perdeu e te culpa. De crer em ti quando todos duvidam, e para esses, no entanto, achar uma desculpa. Se és capaz de esperar sem te desesperares, e enganado, não mentir ao mentiroso. Ou, sendo odiado, ao ódio te esquivares, e não ser bom demais nem pretensioso. Se és capaz de pensar, sem que a isso só te atires, e de sonhar, sem fazer dos sonhos teus senhores. Se, encontrando a Desgraça e o Triunfo, tratar da mesma forma a esses dois impostores. Se és capaz de sofrer a dor de ver transformadas em armadilhas as verdades que disseste. E estraçalhadas as coisas por que deste a vida, e refazê-las com o bem pouco que te resta. Se és capaz de arriscar numa única parada tudo quanto ganhaste em toda tua vida. E perder e, ao perder, resignado e sem dizer nada, recomeçar do início De forçar coração, nervos, músculos, tudo, e dar seja o que for que neles ainda existe. E persistir quando, exausto, ainda te resta a vontade que te ordena: Persiste! Se és capaz de, entre a plebe não te corromperes, e entre reis não perder a naturalidade. E de amigos, bons ou maus, te defenderes, e a ambos poder ser de alguma utilidade. Se és capa...

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Radiation Response of Mouse Lymphoid and Myeloid Cell Lines. Part I. Sensitivity to Killing by Ionizing Radiation, Rate of Loss of Viability, and Cell Type of Origin

Cited by 45 publications

References 34 publications

DNA damage triggers a prolonged p53-dependent G1 arrest and long-term induction of Cip1 in normal human fibroblasts.

DNA damage triggers a prolonged p53-dependent G1 arrest and long-term induction of Cip1 in normal human fibroblasts.

Increasing the susceptibility of the rat 208F fibroblast cell line to radiation-induced apoptosis does not alter its clonogenic survival dose-response

Avaliação dos efeitos da inibição de cadeias inflamatórias e da suplementação exógena de CXCL12 na hematopoiese de modelos experimentais expostos a doses letais ou subletais de radiação gama

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