Prevention of adriamycin-induced mdr1 gene amplification and expression in mouse leukemia cells by simultaneous treatment with the anti-recombinogen bromovinyldeoxyuridine.

The anti-recombinogenic substance (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU) was tested for its ability to prevent adriamycin-induced mdr1 gene amplification and expression in mouse leukemia cells in vitro. F4-6 cells that were treated with stepwise enhanced doses of adriamycin acquired resistance against adriamycin. While 20 ng/ml adriamycin showed strong toxic effects in sensitive cells, the same dose was tolerated at the end of the long-term experiment following treatment with stepwise enhanced doses of adriamycin. In parallel experiments, 0.5 or 1 microg/ml BVDU was given together with adriamycin. BVDU prevented the formation of resistance against adriamycin treatment. Using differential PCR, the signal intensity of the mdr1a-specific band appeared markedly increased in adriamycin-resistant cells, while the signal intensities of the adriamycin + BVDU-treated cells resembled the intensity ratio of the untreated control cells. Beyond that, in resistant F4-6 cells increased expression of mdr genes was demonstrated by Northern blot analysis.

[1]  R. Fahrig.  Anti-recombinogenic and convertible co-mutagenic effects of (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU) and other 5-substituted pyrimidine nucleoside analogs in S. cerevisiae MP1. , 1996, Mutation research.

[2]  C. Slapak,et al.  Expression of c-fos precedes MDR3 in vincristine and adriamycin selected multidrug resistant murine erythroleukemia cells. , 1996, Biochemical and Biophysical Research Communications - BBRC.

[3]  A. Steinkamp-Zucht,et al.  Induction or suppression of SV40 amplification by genotoxic carcinogens, non-genotoxic carcinogens or tumor promoters. , 1996, Mutation research.

[4]  S. Cohn,et al.  Expression of the gene for multidrug-resistance-associated protein and outcome in patients with neuroblastoma. , 1996, The New England journal of medicine.

[5]  M. Haber,et al.  Expression of the multidrug resistance-associated protein (MRP) gene correlates with amplification and overexpression of the N-myc oncogene in childhood neuroblastoma. , 1994, Cancer research.

[6]  T. Kunkel,et al.  International Commission for Protection Against Environmental Mutagens and Carcinogens. Deoxyribonucleoside triphosphate levels: a critical factor in the maintenance of genetic stability. , 1994, Mutation research.

[7]  B. Glauner,et al.  Quantification of Cytotoxicity by Cell Volume and Cell Proliferation , 1993 .

[8]  M. Gottesman.  How cancer cells evade chemotherapy: sixteenth Richard and Hinda Rosenthal Foundation Award Lecture. , 1993, Cancer research.

[9]  A. Bhushan,et al.  Expression of c-fos in human and murine multidrug-resistant cells. , 1992, Molecular pharmacology.

[10]  M. Volm,et al.  Time course of MDR gene amplification during in vivo selection for doxorubicin-resistance and during reversal in murine leukemia L 1210. , 1991, Anticancer Research.

[11]  B. Kopnin,et al.  Karyotype and Amplicon Evolution during Stepwise Development of Multidrug Resistance in Djungarian Hamster Cell Lines , 1991 .

[12]  J. M. Ford,et al.  Pharmacology of drugs that alter multidrug resistance in cancer. , 1990, Pharmacological reviews.

[13]  D. Cohen,et al.  Structural analysis of the mouse mdr1a (P-glycoprotein) promoter reveals the basis for differential transcript heterogeneity in multidrug-resistant J774.2 cells , 1990, Molecular and cellular biology.

[14]  H. Takano,et al.  Inverse correlation between expression of multidrug resistance gene and N-myc oncogene in human neuroblastomas. , 1990, Cancer research.

[15]  T. Braun,et al.  Differential expression of myogenic determination genes in muscle cells: possible autoactivation by the Myf gene products. , 1989, The EMBO journal.

[16]  E. Liu,et al.  Detection of amplified oncogenes by differential polymerase chain reaction. , 1989, Oncogene.

[17]  S. Horwitz,et al.  Differential overexpression of three mdr gene family members in multidrug-resistant J774.2 mouse cells. Evidence that distinct P-glycoprotein precursors are encoded by unique mdr genes. , 1989, The Journal of biological chemistry.

[18]  G. Wahl,et al.  The importance of circular DNA in mammalian gene amplification. , 1989, Cancer research.

[19]  B. Kopnin,et al.  [Gene amplification in murine leukemia cells with multiple drug resistance acquired in vivo]. , 1987, Genetika.

[20]  P. Chomczyński,et al.  Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. , 1987, Analytical biochemistry.

[21]  J. Broach,et al.  Site-specific recombination promotes plasmid amplification in yeast , 1986, Cell.

[22]  R T Schimke,et al.  Overreplication and recombination of DNA in higher eukaryotes: potential consequences and biological implications. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[23]  R. Haynes.  Molecular mechanisms in genetic stability and change: the role of deoxyribonucleotide pool balance. , 1985, Basic life sciences.

[24]  W. Ostertag,et al.  Duplicated alpha-chain genes in Hopkins-2 haemoglobin of man and evidence for unequal crossing over between them. , 1972, Nature: New biology.