Effects of heat and radiation on mammalian cells

Konings, Awt

doi:10.1016/1359-0197(87)90103-2

Cited by 18 publications

(13 citation statements)

References 52 publications

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“…Proteotoxicity (damage to proteins caused by chemical or physical agents; Hightower, 1991) is suggested to be involved in hyperthermic cell killing (Dewey, 1989;Konings, 1987;Lepock et al, 1988;Massicotte-Nolan et al, 1981), the induction of thermotolerance (Lee and Hahn, 1988), and the induction of heat shock protein synthesis (Hightower, 1991). The results presented in this report support this hypothesis and suggest involvement of the proteins in the PF in these processes.…”

Section: Discussionsupporting

confidence: 86%

Heat induced protein denaturation in the particulate fraction of hela S3 cells: Effect of thermotolerance

Burgman

Konings

1992

Journal Cellular Physiology

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In this study we investigated the effect of heat on the proteins of the particulate fraction (PF) of HeLa S3 cells using electron spin resonance (ESR) and thermal gel analysis (TGA). ESR detects overall conformational changes in proteins, while TGA detects denaturation (aggregation due to formation of disulfide bonds) in specific proteins. For ESR measurements the -SH groups of the proteins were labelled with a maleimido bound spin label (4-maleimido-tempo). The sample was heated inside the ESR spectrometer at a rate of 1 degree C/min. ESR spectra were made every 2-3 degrees C between 20 degrees C and 70 degrees C. In the PF of untreated cells conformational changes in proteins were observed in three temperature stretches: between 38 and 44 degrees C (transition A, TA); between 47 and 53 degrees C (transition B, TB); and above 58 degrees C (transition C, TC). With TGA, using the same heating rate, we identified three proteins (55, 70, and 90 kD) which denatured during TB. No protein denaturation was observed during TA, while during TC denaturation of all remaining proteins in the PF occurred. When the ESR and TGA measurements were done with the PF of (heat-induced) thermotolerant cells, TA was unchanged while TB and TC started at higher temperatures. The temperature shift for the onset of these transitions correlated with the degree of thermotolerance that was induced in the cells. These results suggest that protection against heat-induced denaturation of proteins in the PF is involved in heat induced thermotolerance.

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Section: Discussionsupporting

confidence: 86%

Heat induced protein denaturation in the particulate fraction of hela S3 cells: Effect of thermotolerance

Burgman

Konings

1992

Journal Cellular Physiology

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“…ionizing radiation (Konings 1987) and UV irradiation (Sakkers et al, 1993)], we also studied the removal of Pt-DNA adducts. The percentage adducts removed was not always found to be significantly decreased in the heated cells.…”

Section: Discussionmentioning

confidence: 99%

Mechanism of hyperthermic potentiation of cisplatin action in cisplatin-sensitive and -resistant tumour cells

Hettinga

Lemstra²,

Meijer³

et al. 1997

Br J Cancer

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Summary In this study, the mechanism(s) by which heat increases cis-diamminedichloroplatinum (cisplatin, cDDP) sensitivity in cDDPsensitive and -resistant cell lines of murine as well as human origin were investigated. Heating cells at 430C during cDDP exposure was found to increase drug accumulation significantly in the cDDP-resistant cell lines but had little effect on drug accumulation in the cDDP-sensitive cell lines. DNA adduct formation, however, was significantly increased in all cell lines studied. Furthermore, ongoing formation of platinum (Pt)-DNA adducts after the end of cDDP treatment was enhanced and/or adduct removal was decreased in heated cells, resulting in relatively more DNA damage remaining at 24 h after the end of cDDP exposure. Correlation plots with survival revealed weak correlations with cellular Pt accumulation (r2 = 0.59) and initial Pt-DNA adduct formation (r2 = 0.64). Strong correlations, however, were found with Pt-DNA adducts at 6 h (r2 = 0.97) and 24 h (r2 = 0.89) after the incubation with the drug. In conclusion, the mechanism by which heat sensitizes cells for cDDP action seems to be the sum of multiple factors, which comprise heat effects on accumulation, adduct formation and adduct processing. This mechanism did not seem to differ between cDDP-sensitive and -resistant cells, emphasizing the potential of hyperthermia to reduce cDDP resistance.Keywords: thermochemosensitization; cisplatin resistance; cisplatin accumulation; cisplatin-DNA adducts; adduct repair Hyperthermia can strongly potentiate the cytotoxic action of cisdiamminedichloroplatinum (cisplatin, cDDP) both in vitro and in vivo (reviewed by Engelhardt, 1987). In addition, relatively high heat doses (above 42°C) can (partly) reverse in vitro acquired cDDP resistance (Wallner et al, 1986;Herman et al, 1988;Mansouri et al, 1989;Konings et al, 1993;Hettinga et al, 1994). Resistance to cDDP is a major problem in the clinic and limits the success of this drug. Thus, the combined use of heat and cDDP appears to be an interesting possibility to minimize this problem. The mechanism by which cells become resistant to cDDP has been extensively studied by numerous groups and has been found to be multifactorial (reviewed by Andrews and Howell, 1990), including (combinations of) decreased drug accumulation, increased detoxification of the drug via glutathione (GSH) metabolism or metallothioneins, decreased drug-DNA adduct formation and increased repair of the drug-induced DNA damage. The mechanism(s) by which hyperthermia sensitizes cells to cDDP is (are) less clear. Altered platinum (Pt) accumulation, total Pt-DNA adduct and DNA cross-link formation and/or repair of DNA damage have been reported as a result of combined heat and cDDP treatments (Meyn et al, 1980;Wallner et al, 1986;Herman et al, 1988Herman et al, , 1989Herman et al, , 1990Mann et al, 1988;Mansouri et al, 1989;Eichholtz-Wirth and Hietel, 1990;Los et al, 1993;Takahashi et al, 1993;Ohno et al, 1994). However, the published data are rather contradictory, and in most ...

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“…Hyperthermia is a powerful tool to enhance the cell killing effects of radiation (Konings, 1987) and many anti-neoplastic agents (Engelhardt, 1987). However, heat pretreatment leads to a reduction in the toxic action of some drugs.…”

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confidence: 99%

Hyperthermia, thermotolerance and topoisomerase II inhibitors

Kampinga

1995

Br J Cancer

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Summary The cytoxicity of both intercalating (m-AMSA) and non-intercalating (VP16, VM26) topoisomerase II-targeting drugs is thought to occur via trapping DNA topoisomerase II on DNA in the form of cleavable complexes. First, analysis of cleavable complexes (detected as DNA double-strand breaks) by pulsed-field gel electrophoresis confirmed the correlation between cleavable complex formation and cytotoxicity of three topoisomerase-targeting drugs in HeLa S3 cells (the order of effects being VM26> m-AMSA>VP16). In contrast to many antineoplastic agents, hyperthermic treatments were found to protect cells against the toxicity of all three topoisomerase II drugs. Hyperthermia treatment does not alter drug accumulation but reduces the ability of the drug-topoisomerase II complex to form the cleavable complexes. Nuclear protein aggregation induced by heat at the sites of topoisomerase II-DNA interaction may explain such an effect. In thermotolerant cells, the toxic effects of VP16 but not m-AMSA were reduced. For both drugs, however, the status of thermotolerance did not affect cleavable complex formation by the drugs. Thus, protection against VP-16 toxicity seems not to be associated with heat-induced activation of the P-gp 170 pump or altered topoisomerase II-DNA interactions. Rather, a protective (heat shock protein mediated?) mechanism against non-intercalating topoisomerase II drugs seems to occur at a stage after DNA-drug interaction. Finally, heat treatment before topoisomerase II drug treatment reduced toxicity and cleavable complex formation in thermotolerant cells to about the same extent as in non-tolerant cells, consistent with the presumption of nuclear protein aggregation being responsible for this effect.

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Effects of heat and radiation on mammalian cells

Cited by 18 publications

References 52 publications

Heat induced protein denaturation in the particulate fraction of hela S3 cells: Effect of thermotolerance

Heat induced protein denaturation in the particulate fraction of hela S3 cells: Effect of thermotolerance

Mechanism of hyperthermic potentiation of cisplatin action in cisplatin-sensitive and -resistant tumour cells

Hyperthermia, thermotolerance and topoisomerase II inhibitors

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