Melphalan resistant human ovarian tumour cells are cross-resistant to photons, but not to high LET neutrons

Britten, Richard A.; Warenius, Hilmar M.; White, R.E.; Browning, Paul; Green, J.A.

doi:10.1016/0167-8140(90)90116-e

Cited by 20 publications

(4 citation statements)

References 21 publications

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“…Radical scavenging in aerobic cells requmres a greater GSH concentration than has nd rats in -1 J J Eady eti a 1093 ever been achieved in any cell, while other protective mechanisms need only a low GSH concentration so that they are operating close to maximally under normal conditions (Bump and Brown, 1990). However, extreme GSH depletion may reduce the influence of such mechanisms, particularly enzymatic protection against hydroperoxides, and it is the reduction of this function that is considered responsible for icreased aerobic radiosensitivity reported following extreme GSH depletion (Dethmers and Meister, 1981;Astor et al, 1984;Biaglow et al, 1984;van der Schans et al, 1986;Britten et al, 1990;Lehnert et al, 1990). Radiation-produced peroxide is reduced, and so detoxified, principally by GSH peroxidase, with catalase accounting for the remaining inactivation, so that peroxide is not thought to be responsible for any increased radiosensitivity under aerobic conditions (Biaglow et al, 1992).…”

Section: Dioaimentioning

confidence: 99%

“…Increased aerobic radiosensitisation following BSO exposure has been reported for a human lung adenocarcinoma , HeLa (van der Schans et al, 1986), V79 cells (Astor et al, 1984), human lymphoid cells (Dethmers and Meister, 1981), and drug-resistant variants both of a human breast line (Lehnert et al, 1990) and of a human ovarian cell line (Britten et al, 1990) (Debieu et al, 1985), whilst many others have found that GSH depletion resulted in radiosensitisation only under hypoxic conditions, though the degee of sensitisation produced is highly variable (Bump and Brown, 1990).…”

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confidence: 99%

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Glutathione determination by the Tietze enzymatic recycling assay and its relationship to cellular radiation response

Eady

Orta²,

Dennis³

et al. 1995

Br J Cancer

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S_rnuary Large fluctuations in glutathione content were observed on a daily basis using the Tietze enzyme recycling assay in a panel of six human cell lines of varying radiosensitivity. Glutathione content tended to increase to a maximum during exponential cell proliferation, and then decreased at different rates as the cells approached plateau phase. By reference to high-performance liquid chromatography and flow cytometry of the fluorescent bimane derivative we were able to verify that these changes were real. However, the Tietze assay was occasionally unable to detect glutathione in two of our cell lines (MGH-Ul and AT5BIVA), although the other methods indicated its presence. The existence of an inhibitory activity responsible for these anomalies was confirmed through spiking our samples with known amounts of glutathione. We were unable to detect a direct relationship between cellular glutathione concentration and aerobic radiosensitivity in our panel of cell lines.Keyworid glutathione; radiosensitivity; Tietze assay; high-performance liquid chromatography For at least the past decade the tripeptide sulphydryl compound glutathione (GSH) has been the subject of intensive investigation regarding its role in mediating both radiationand drug-induced responses in living cells. GSH has been proposed to act in a vast number of different cellular processes, amongst them the maintenance of a suitable intracellular reductive environment, protection against harmful xenobiotics, a catalyst of or reactant in several metabolic schemes and an intracellular store of cysteine (Nygaard and Simic, 1983;Mitchell and Russo, 1987). Its potential importance for radiobiology has been recognised ever since the development of the competition model for radiation cell killing, a mathematical consequence of the reaction rates for competing reactions (Alper and Howard-Flanders, 1956). DNA radicals produced by irradiation are considered to be subject to a competition between oxidising (or electronaffinic) agents, leading to damage fixation and ultimate cell death, and reducing species (such as sulphydryl compounds) which, through hydrogen atom donation would facilitate damage repair and so lead to continued cell viability, against a background of the intramolecular decay of DNA radicals to render them non-restorable (Koch, 1983). Since the rate of reaction between oxygen and DNA radicals is far greater than that between GSH and DNA radicals (Bump and Brown, 1990), the competition theory predicts that under normal aerobic conditions the former reaction would dominate, rendering unimportant any changes in GSH content. However GSH may nevertheless play a significant role in the aerobic radiation response, its protective effects mediated through other processes limiting radiation damage, for instance the detoxification of radiation-induced hydroperoxides (Dethmers and Meister, 1981;Biaglow et al., 1984).Cells may be depleted of GSH by treatment with the specific enzyme inhibitor DL-buthionine-S,R-sulphoximine (BSO) which prevents GSH synthesi...

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Section: Dioaimentioning

confidence: 99%

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confidence: 99%

Glutathione determination by the Tietze enzymatic recycling assay and its relationship to cellular radiation response

Eady

Orta²,

Dennis³

et al. 1995

Br J Cancer

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“…Aerobic radiosensitization after BSOmediated inhibition of GSH synthesis has been demonstrated in human lymphoid cell lines, 39 drug-resistant variants of a human breast line, 40 a human ovarian line, 41 the human lung line A549, 42 and V79 cells. 43 Mirkovic et al 44 demon- strated that resistance to radiation-induced apoptosis in Bcl-2-expressing mouse lymphoma cells is reversed by depleting cellular thiols.…”

Section: Discussionmentioning

confidence: 99%

Cisplatin and radiation sensitivity in human head and neck squamous carcinomas are independently modulated by glutathione and transcription factor NF-?B

et al. 2000

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“…OAW42MER (Britten et al, 1990) and A2780cp8 (Beherens et al, 1987) were used in the study. The A2780d cell clone, which was selected in culture without drug exposure was also used.…”

Section: Cell Lines and Growth Inhibition Assaymentioning

confidence: 99%

Activity of a trinuclear platinum complex in human ovarian cancer cell lines sensitive and resistant to cisplatin: cytotoxicity and induction and gene-specific repair of DNA lesions

et al. 2001

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Summary A collateral sensitivity or a very modest cross-resistance to BBR 3464 was found in 2 ovarian cancer cell lines with experimentally induced resistance to cisplatin. Loss of mismatch repair proteins (hMLH1, hPMS2) or overexpression of nucleotide excision repair proteins (ERCC1) was not detrimental for the cellular sensitivity to BBR 3464. Moreover, interesting differences in the kinetics of formation and removal of DNA lesions at the single-gene (N-ras) level were observed between BBR 3464 and CDDP.

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Melphalan resistant human ovarian tumour cells are cross-resistant to photons, but not to high LET neutrons

Cited by 20 publications

References 21 publications

Glutathione determination by the Tietze enzymatic recycling assay and its relationship to cellular radiation response

Glutathione determination by the Tietze enzymatic recycling assay and its relationship to cellular radiation response

Cisplatin and radiation sensitivity in human head and neck squamous carcinomas are independently modulated by glutathione and transcription factor NF-?B

Activity of a trinuclear platinum complex in human ovarian cancer cell lines sensitive and resistant to cisplatin: cytotoxicity and induction and gene-specific repair of DNA lesions

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