Dominance of resistance to the alkylating agent 1,2:5,6-dianhydrogalactitol in P388 mouse lymphoma hybrid cells

Pályi, I; Bence, Judit; Szikla, K.; Hullán, Lehel

doi:10.1007/bf00258456

Cancer Chemother. Pharmacol.

1989

DOI: 10.1007/bf00258456

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Dominance of resistance to the alkylating agent 1,2:5,6-dianhydrogalactitol in P388 mouse lymphoma hybrid cells

I Pályi¹,

Judit Bence

K. Szikla

et al.

Abstract: Cultured P388/S mouse lymphoma cells resistant to 5-bromodeoxyuridine (BUdR) and deficient in thymidine kinase (TK-) were fused with P388/DAG cells resistant to 1,2:5,6-dianhydrogalactitol (DAG), an anticancer alkylating agent, and to 6-thioguanine (6-TG) and deficient in hypoxanthine phosphoribosyl-transferase (HPRT-). Sensitivity to DAG in the hybrid line was very close to that in the P388/DAG line, which means that resistance to DAG was inherited in a quasi-dominant manner. Hybrid cells showed cross-resista… Show more

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1992

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Cited by 2 publications

References 25 publications

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Dominant expression of multidrug resistance in intraspecific murine lymphoma hybrid cells

Pályi¹,

Turi

Hullán

et al. 1994

Cancer Chemother. Pharmacol.

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Cultured P388/VCR mouse lymphoma cells resistant to vincristine (VCR) and to 5-bromodeoxyuridine (BUdR) and deficient in thymidine kinase (TK-) were fused with P388/DAG cells resistant to 1.2:5,6-dianhydrogalactitol (DAG), an anticancer alkylating agent, and to 6-thioguanine (6-TG) and deficient in hypoxanthine phosphoribosyl-transferase (HPRT-). The hybrid cells expressed multidrug resistance (MDR), i.e., resistance to VCR and cross-resistance to Adriamycin (ADM) and actinomycin D (Act. D), in a dominant manner. The presence of glycoprotein p170, the MDR gene product, was detected in the hybrid cells. Resistance to DAG was also expressed dominantly, whereas cross-resistance to dibromodulcitol (DBD), a chemically related anticancer drug, was slight.

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Dominant expression of multidrug resistance in intraspecific murine lymphoma hybrid cells

Pályi¹,

Turi

Hullán

et al. 1994

Cancer Chemother. Pharmacol.

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Benzamide potentiation of the cytotoxicity of bifunctional galacticol in resistant P388 leukemia correlates with inhibition of DNA ligase II

Institoris

Fox

Pályi³

1992

Cancer Chemother. Pharmacol.

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Benzamide (BA) enhances the cytotoxicity of 1,2:5,6-dianhydrogalactitol (DAG) in resistant P388 leukemia cell lines but not in the sensitive parent line. To examine the reason for this difference in response, we carried out an alkaline elution assay using proteinase K to study DNA interstrand cross-linking. At early time points, equal concentrations of DAG produced the same level of interstrand cross-linking (ICL) in the resistant and sensitive P388 leukemic cells, although marked differences were observed in their cytotoxicity toward the two cell lines. In the sensitive cells, neither the amount of DNA cross-linking nor the cytotoxicity changed during the observation period (38 h) in either the presence or the absence of BA. In contrast, the elution rate of the DNA of DAG-treated resistant cells increased with time and had reached the control levels by 38 h. However, when these cells were postincubated with BA for 38 h, the elution rate of DNA was much faster than that observed for the untreated resistant cells, indicating an accumulation of DNA single-strand breaks (SSB). The SSB accumulation caused by BA was associated with an inhibition of the activity of ligase II enzyme, which was stimulated when resistant cells were treated with DAG alone. The potentiating effect of BA on the resistant cells can thus be related to the inhibiting action of BA on the DNA-rejoining enzyme, ligase II. The lack of sensitization by BA of the DAG-treated parent cell line may be attributable to the absence of DNA-SSB formation, which is necessary for ligase II activation through the stimulation of poly(ADP-ribose) synthesis.

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Dominance of resistance to the alkylating agent 1,2:5,6-dianhydrogalactitol in P388 mouse lymphoma hybrid cells

Cited by 2 publications

References 25 publications

Dominant expression of multidrug resistance in intraspecific murine lymphoma hybrid cells

Dominant expression of multidrug resistance in intraspecific murine lymphoma hybrid cells

Benzamide potentiation of the cytotoxicity of bifunctional galacticol in resistant P388 leukemia correlates with inhibition of DNA ligase II

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