1995
DOI: 10.1038/bjc.1995.440
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p53-independent death and p53-induced protection against apoptosis in fibroblasts treated with chemotherapeutic drugs

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Cited by 46 publications
(21 citation statements)
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“…An effect on ADP(ribose) metabolism is most probable, given that 3-AB (1 mM) can completely inhibit a Potentiation of temozolomide by O6-BG and 3-AB SR Wedge et al 1034 50% reduction in cellular NAD produced by treatment with 2 mM temozolomide (Boulton et al, 1995). The association between DNA strand breakage and the inhibition of PARP with 3-AB, however, remains controversial (Boulton et al, 1995), and it is possible that the enhancement of temozolomide cytotoxicity by 3-AB could be related to the inhibition of acceptor protein ADP-(ribosyl)ation, particularly if such proteins regulate cell cycle progression or apoptosis in response to DNA damage (Kastan et al, 1991;Nosseri et al, 1994;Malcomson et al, 1995). The magnitude by which methylation and chloroethylation cytotoxicity was enhanced by 06-BG did not clearly correlate with AGT activity, although resistance to both agents can be multifactorial and dependent on factors other than at the level of DNA repair.…”
Section: Discussionmentioning
confidence: 99%
See 1 more Smart Citation
“…An effect on ADP(ribose) metabolism is most probable, given that 3-AB (1 mM) can completely inhibit a Potentiation of temozolomide by O6-BG and 3-AB SR Wedge et al 1034 50% reduction in cellular NAD produced by treatment with 2 mM temozolomide (Boulton et al, 1995). The association between DNA strand breakage and the inhibition of PARP with 3-AB, however, remains controversial (Boulton et al, 1995), and it is possible that the enhancement of temozolomide cytotoxicity by 3-AB could be related to the inhibition of acceptor protein ADP-(ribosyl)ation, particularly if such proteins regulate cell cycle progression or apoptosis in response to DNA damage (Kastan et al, 1991;Nosseri et al, 1994;Malcomson et al, 1995). The magnitude by which methylation and chloroethylation cytotoxicity was enhanced by 06-BG did not clearly correlate with AGT activity, although resistance to both agents can be multifactorial and dependent on factors other than at the level of DNA repair.…”
Section: Discussionmentioning
confidence: 99%
“…These may include drug-detoxification mechanisms, involving glutathione-S-transferase (Smith et al, 1989;Waxman, 1990) or metallothionine (Kelley et al, 1988). In addition, the p53 injury-response pathway, which induces G, arrest and/or apoptosis in response to DNA damage (Kastan et al, 1991;Malcomson et al, 1995), may also contribute to drug resistance following mutational events or overexpression of bcl-2 (Miyashita and Reed, 1992;Fairburn et al, 1994).…”
Section: Discussionmentioning
confidence: 99%
“…Both MCF-7 10 nM 126 and MCF-7 10 µM 126 variants exhibit greatly enhanced levels of wt p53. Elevated p53 may promote survival in the presence of cytotoxins by arresting cells in the G 1 cell cycle phase, permitting repair of damaged DNA such that cells, rescued from the apoptotic pathway, are offered a growth advantage in the presence of the survival signal provided by enhanced bcl-2 expression (Malcomson et al, 1995;Kinzler and Vogelstein, 1994). However, sensitivity to 2-(4-aminophenyl)benzothiazoles does not depend upon functional p53 or bcl-2 expression as exemplified by the equi-sensitive human breast carcinoma cell line MDA 468.…”
Section: Discussionmentioning
confidence: 99%
“…Based on cell line experiments and the knowledge of cytotoxic agents' ability to induce apoptosis, it has been proposed that loss of p53 indicate resistance to treatment (35,36). However, other experiments showed the existence of a p53 independent way to apoptosis (37) and at the same time we reported on results that suggested a benefit of chemotherapy with CMF among premenopausal breast cancer patients with accumulated p53, randomized to adjuvant chemotherapy or postoperative radiotherapy (11). This study was small but, nevertheless, we thought these results were promising and motivated further studies.…”
Section: Discussionmentioning
confidence: 99%