Hyperthermic Radiosensitization of Synchronous Chinese Hamster Cells: Relationship between Lethality and Chromosomal Aberrations

Dewey, William C.; Sapareto, Stephen A.; Betten, David A.

doi:10.2307/3574926

Cited by 147 publications

(49 citation statements)

References 22 publications

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“…A log-linear relationship similar to that shown in Figure 3 between survival and chromatid aberration frequency was shown in x-irradiated CHO cells by Dewey et al (1978). Their results suggested that only one aberration per cell is required for cell death and that chromatid type aberrations appeared to be as lethal as the chromosome type.…”

Section: Discussionsupporting

confidence: 52%

“…7he frequency of chromosome aberrations and cell killing Although there is a well-established relationship between chromosomal aberrations and radiationinduced cell death (e.g. Dewey et al, 1978), the contribution of chromosomal aberrations to cell lethality induced by chemical agents has been studied to a much lesser extent (reviewed by Scott, 1977). Platinum compounds were not included in these studies nor in the quantitative comparison of cytogenetic effects of x-rays and anti-tumour drugs by Parkes & Scott (1982).…”

Section: Discussionmentioning

confidence: 99%

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The mode of action of cis dichloro-bis (isopropylamine) trans dihydroxy platinum IV (CHIP) studied by the analysis of chromosome aberration production

Bocian¹,

Laverick²,

Nias³

1983

Br J Cancer

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Summary The induction of chromosome damage by the Platinum complex CHIP in Chinese hamster ovary (CHO) cells has been studied, together with the relationship between cell survival and aberration frequency. The type and frequency of chromosome aberrations observed in asynchronous and G, phase treated cells indicated a similar mode of action to that of bifunctional alkylating agents. A log-linear relationship was observed between the frequency of chromatid aberrations (excluding gaps) and the level of survival after CHIP treatment, with approximately one aberration per cell corresponding to 37% survival.Cis dichloro-bis (isopropylamine) trans dihydroxy platinum IV-CHIP-is one of the new platinum co-ordination complexes in the group of potential antitumour agents, whose cytotoxic action has now been studied extensively. It can be compared with another platinum complex cis-dichloro-bis (cyclopentylamine) platinum (II), PAD, which although insoluble in water was found to have a high antitumour activity and a large therapeutic index (235), (Connors et al., 1972). In contrast, CHIP is highly water soluble and this has encouraged further investigation into its mode of action.Results from several workers indicate that DNA is the primary intracellular target for the cytotoxic action of the platinum complexes, where inter-and intra-strand crosslinks are produced (Roberts & Pascoe, 1972;Kelman et al., 1977). These effects of platinum complexes on DNA point to a similar mode of action to that observed with bifunctional alkylating agents; i.e. the production of "delayed type" chromosome aberrations as a result of DNA synthesis on a damaged template (Bender et al., 1974).Studies were undertaken to examine this possibility and to understand better the mechanism underlying the cytotoxic action of CHIP. In this paper the results of the investigation of the production of chromosome aberrations by CHIP in

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Section: Discussionsupporting

confidence: 52%

Section: Discussionmentioning

confidence: 99%

The mode of action of cis dichloro-bis (isopropylamine) trans dihydroxy platinum IV (CHIP) studied by the analysis of chromosome aberration production

Bocian¹,

Laverick²,

Nias³

1983

Br J Cancer

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“…1B). The increase in the relative fraction of slowly rejoined IR-induced DNA DSB leads to an increased probability for the persistence of unrejoined DNA DSB and/or the generation of misrejoined DNA DSB, both leading to lethal chromosomal aberrations (1,5,42). In H2AX À/À MEFs, it has been shown that the initial recruitment of 53BP1 to sites of DNA damage is independent of H2AX, whereas the persistence of 53BP1 IRIF is dependent on H2AX.…”

Section: Discussionmentioning

confidence: 99%

Heat-Induced Perturbations of DNA Damage Signaling Pathways are Modulated by Molecular Chaperones

Laszlo

Fleischer

2009

Cancer Research

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Heat is one of the most potent radiosensitizers known. Several randomized trials have shown that hyperthermia is a good adjuvant for radiotherapy at several different cancer sites. However, the mechanism(s) involved in the interaction of heat and radiation that lead to radiosensitization remain to be elucidated. In this report, we have determined that heat induces perturbations in some of the earliest events in the cellular response to DNA damage induced by ionizing radiation. We studied the effect of heat on the formation of complexes containing ;-H2AX/MDC1/53BP1 in heated-irradiated cells. We found that the formation of this complex was delayed in heated-irradiated cells, in a heat but not radiation dose-dependent manner. The length of the heat-induced delay of complex formation was attenuated in thermotolerant and heat radiosensitization-resistant cells. The length of the delay of ;-H2AX/MDC1/53BP1 complex formation correlated with the magnitude of heat radiosensitization and was modulated by the molecular chaperone Hsc70. Heat radiosensitization was attenuated in 53BP1-null cells, implying that the delay of the formation of the ;-H2AX/MDC1/53BP1 complex plays a role in heat radiosensitization. Heat also induced a delay of events in the DNA damage response that are downstream from 53BP1. Our results support the notion that heat-induced perturbations in the earliest events of the cellular response to ionizing radiation-induced DNA damage play a role in heat radiosensitization. [Cancer Res 2009;69(5):2042-9]

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“…It is used in combination with chemo-and/or radiotherapy since it is has been shown to enhance the anti-cancer effects of both therapies (Gonzalez Gonzalez et al, 1995;Van Der Zee et al, 2002;Crezee et al 2009). Many in vitro studies on the combination of hyperthermia and radiation have shown a synergistic interaction between the two modalities, especially at higher temperatures (above 42ºC) (Dewey et al, 1978;Roti Roti, 2004;Raaphorst et al, 1991). This interaction is believed to result from inhibition of repair of radiation-induced DNA damage by hyperthermia Hildebrandt et al, 2002).…”

Section: Hyperthermiamentioning

confidence: 99%

Radiosensitization with Hyperthermia and Chemotherapeutic Agents: Effects on Linear-Quadratic Parameters of Radiation Cell Survival Curves

Franken¹,

Hovingh²,

Oei³

et al. 2012

Current Topics in Ionizing Radiation Research

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Hyperthermic Radiosensitization of Synchronous Chinese Hamster Cells: Relationship between Lethality and Chromosomal Aberrations

Cited by 147 publications

References 22 publications

The mode of action of cis dichloro-bis (isopropylamine) trans dihydroxy platinum IV (CHIP) studied by the analysis of chromosome aberration production

The mode of action of cis dichloro-bis (isopropylamine) trans dihydroxy platinum IV (CHIP) studied by the analysis of chromosome aberration production

Heat-Induced Perturbations of DNA Damage Signaling Pathways are Modulated by Molecular Chaperones

Radiosensitization with Hyperthermia and Chemotherapeutic Agents: Effects on Linear-Quadratic Parameters of Radiation Cell Survival Curves

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