A comparison of adriamycin and mAMSA in vitro: Cell lethality and SCE studies

West, Catharine M L; Stratford, I J; Barrass, Nigel; Smith, Elizabeth E.

doi:10.1038/bjc.1981.278

Cited by 26 publications

(6 citation statements)

References 11 publications

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“…Our results are also consistent with observations made by West et al (1981) to 0.2 gM of m-AMSA for 1 hr, demonstrated distribution patterns with a large variance, similar to the ones we observed at 1 #M m-AMSA. In similar studies, Kao-Shan et al (1984) studied cytogenetic effects of m-AMSA in human lymphocytes, observing potent SCE induction with doses ranging from 0.005 #g/ml to 1.0 ~g/ml and exposure times from 48 to 72 hr.…”

Section: Discussionsupporting

confidence: 82%

“…Huang et al (1983) reported that camptothecin is a very potent inducer of SCEs. West et al (1981) and Kao-Shan et al (1984) observed strong SCE induction by m-AMSA, and Singh and Gupta (1983) also observed very high induction of SCE levels with VM-26. Due to variations in cell line, drug exposure time and dose range, however, it is very difficult to compare relative potency on baseline of these agents.…”

Section: Introductionmentioning

confidence: 96%

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Induction of sister chromatid exchanges by inhibitors of topoisomerases

et al. 1986

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To investigate the role of topoisomerases in the production of sister chromatid exchanges, the effects of inhibitors of type I and II topoisomerases on baseline and mutagen-induced sister chromatid exchanges were compared. V79 cells were treated with VM-26 and m-AMSA, known inhibitors of type II topoisomerase, or with camptothecin, the only known inhibitor of type I topoisomerase. We observed that inhibitors of both type I and II topoisomerases induced high levels of sister chromatid exchanges at 10(-6) M, and that the dose-response curves of these drugs were very similar. A clear heterogeneity in the distribution patterns of exchanges induced by inhibitors of topoisomerases was observed. We believe that this heterogeneity in response to these compounds is due to variation in sensitivity within the cell cycle. We also studied interactions of these agents with mitomycin-C and with PUVA (8-methoxypsoralen + UVA), both cross-linking agents and potent sister chromatid exchange inducers, and with x-rays, an agent that induces high levels of DNA strand breaks. No significant change in exchange levels was observed in interactions between topoisomerase inhibition and the levels induced by the agents studied. We conclude that double-strand break prevalence, known to be increased through inhibition of type II topoisomerase, is not the primary mechanism for induction of sister chromatid exchanges. We further conclude that acute inhibition of type I and type II topoisomerases does not influence substantially the induction of exchanges by other agents.

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Section: Discussionsupporting

confidence: 82%

Section: Introductionmentioning

confidence: 96%

Induction of sister chromatid exchanges by inhibitors of topoisomerases

et al. 1986

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“…The similarity between AMSA and ADR as cytotoxic agents has been reported elsewhere [16,20,21]. In an earlier report, we described the cytotoxic effectiveness of ADR to be greatest against FSa cell populations enriched in S-phase [10].…”

Section: Comparison Of Empirical and Theoretical Surviving Fractions supporting

confidence: 74%

Effectiveness of AMSA alone or in combination with radiation on murine fibrosarcoma pulmonary nodules

1984

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The cytotoxic effects in vivo of 4'-(9-acridinylamino) methanesulfon-m-anisidide (AMSA), radiation or both modalities in combination on murine fibrosarcoma (FSa) cells grown as pulmonary tumors were determined. Fourteen days following the i.v. injection of viable FSa cells, recipient mice developed between 100 and 150 visible pulmonary nodules. At that time, tumor-bearing animals were exposed to either single or combined modality treatments, as well as single and fractionated dose regimens. Animals were sacrificed 1 hour after the last treatment. Tumor nodules were excised, made into a single cell suspension and separated on the basis of cell size by centrifugal elutriation. Flow microfluorometry (FMF) was used to determine the cell-cycle parameters and the relative synchrony of the separated populations, as well as the percentage contamination by normal diploid cells in each of the tumor cell populations. Known numbers of viable cells from each elutriator fraction were injected into recipient mice to determine their colony-forming efficiency (CFE). Surviving fractions were determined by comparing the CFEs of treated FSa cells from each of the separated elutriator fractions with those of appropriate untreated controls. Following a single i.v. dose of AMSA (30 mg/kg), populations of cells enriched in S phase were the most sensitive. When a single dose of AMSA was combined with a single dose of radiation (100 rad), there was a marked schedule dependence with the more effective sequence, especially if a 12 hour interval was chosen between doses, being AMSA followed by irradiation. No schedule dependence was observed if both modalities were combined and administered under a fractionated protocol of four fractions of AMSA (5 mg/kg per fraction) and four fractions of radiation (300 rad per fraction). Under these conditions the greatest reduction in CFE was in cell subpopulations most enriched in S and G2 + M phase cells.

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“…Moreover, oxygen deprivation also rendered these cells resistant to 5-FU (Fig. 7B), to etoposide (21), and to amsacrine (53). Taken together, the data suggest that the down-regulation of proapoptotic proteins of the Bcl-2 family by oxygen deprivation is not specific to a single cell type and that it is correlated with resistance to a Sixteen hours of oxygen deprivation resulted in the downregulation of Bid, Bax, and Bad in wt MEFs and of Bax and Bad in Bid KO MEFs but did not affect cell viability in either case (Fig.…”

Section: Hif-1-independent Down-regulation Of Bax and Badmentioning

confidence: 99%