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  • 1
    ISSN: 1572-994X
    Keywords: Epstein-Barr virus ; virus propagation ; HR-1 cells ; EBV ; viral latency ; viral DNA rearrangement
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To understand the mechanism regulating the EBV replication cycle, several sublines were obtained from HR-1 cells by the limiting dilution method. Based on their biochemical and molecular characteristics, these sublines can be categorized into two classes: the high EBV-DNA containing (H) subline and low EBV-DNA containing (L) subline. The amount of EBV proteins, such as EBV polymerases, EBV DNase, EAD, ZEBRA, MA, and VCA, was much higher in H sublines than in L sublines. Only 20% of cells in the H subline express those proteins. In addition to regular EBV DNA restriction enzyme fragments, additional DNA restriction enzyme fragments, as detected by different EBV DNA fragment probes, were found to be present in H sublines but not in L sublines. NoBamH1 W-Z DNA fragment rearrangement, which was the primary reason for ZEBRA expression in a high EBV-DNA containing subline, Clone 5, was found in H sublines. When L sublines were treated with 12-0-tetradecanoylphorbol-13-acetate and sodium butyrate, EBV-specific proteins, including ZEBRA protein, could be induced in cells, but no virus could be detected in the medium. Thus, the lack of EBV production by L sublines is more than the simple lack of expression of ZEBRA protein. L sublines are susceptible to EBV infection and are capable of producing EBV after infection. The importance of the presence of L cells in the H subline for the propagation of EBV in culture is suggested.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1573-904X
    Keywords: etoposide ; DNA topoisomerase II ; amino analogues of etoposide ; KB cells ; cytotoxicity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract A series of 4β-benzoylamino (5-17) derivatives of 4′-O-demethyl-4-desoxypodophyllotoxin and 4β-benzoyl (18-20) derivatives of 4′-O-demethyl podophyllotoxin have been synthesized and evaluated for their inhibitory activity against the human DNA topoisomerase II as well as for their activity in causing cellular protein-linked DNA breakage. Compounds 5-13 and 15-17 are more potent than etoposide in causing DNA breakage, while compounds 9, 10, 13, 14, 16, and 20 are more active than etoposide in their inhibition of the human DNA topoisomerase II. The order for the enzyme inhibitory activity of the derivatives of 4′-O-demethyl-4-desoxypodophyllotoxin is 4β-arylamino 〉 4β-benzylamino 〉 4β-benzoylamino.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1573-904X
    Keywords: etoposide ; DNA topoisomerase II ; anilino analogues of etoposide ; KB cells ; cytotoxicity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract A series of derivatives of 3′,4′ 0,0-didemethylpodophyllotoxin have been synthesized and evaluated for their inhibitor activity against neoplastic cell growth (KB) and against human DNA topoisomerase II as well as for their activity in causing cellular protein-linked DNA breakage. The results show that the compounds possessing a 4β-anilino moiety either unsubstituted or substituted at the para (F, COOCH3, COCH3, CN, CH2CN, NO2) or meta (OH) positions or with an ethylenedioxy moiety showed the same or greater activity than etoposide in causing cellular protein-linked DNA breakage and in inhibiting DNA topoisomerase II. However, compared to the corresponding 4′-0-demethyl analogues, the 3′,4′-O,O-didemethyl compounds have a similar potency in inhibition of DNA topoisomerase II but are less active in causing cellular protein-linked DNA breakage. Complete correlation between the three biological activities–cytotoxicity, inhibition of DNA topoisomerase II, and induction of protein-linked DNA breakage–was also not observed. This supports the possibility that the biological determinants of action among these compounds may be different.
    Type of Medium: Electronic Resource
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