Zidovudine (AZT) resistance in H9 cells due to decreased TK expression is associated with hypermethylation of TK gene

被引：8

作者：

Gröschel, B ^{[1
]}

Höver, G ^{[1
]}

Doerr, HW ^{[1
]}

Cinatl, J ^{[1
]}

机构：

[1] Univ Frankfurt, Inst Med Virol, D-6000 Frankfurt, Germany

来源：

NUCLEOSIDES NUCLEOTIDES & NUCLEIC ACIDS | 2001年 / 20卷 / 4-7期

关键词：

D O I：

10.1081/NCN-100002323

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

AZT resistant human T-lymphoid H9 cells, deficient in TK gene expression, re-expressed TK mRNA and regained the ability to metabolize AZT by exposure to the demethylation agent azacytidine (AzaCd). Cytotoxic and anti-HIV-1 effects of AZT were increased in H9 AZT resistant cells treated with AzaCd when compared to untreated cells. This leads to the assumption that drug induced DNA hypermethylation was involved in the TK gene-silencing mechanism. Our results suggest approaches using modulation of gene methylation for increasing antiviral efficiency of drugs.

引用

页码：487 / 492

页数：6

共 17 条

[1] Pharmacological issues relating to viral resistance [J].

Back, DJ .

INFECTION, 1999, 27 (Suppl 2) :S42-S44

[2]

Cinatl J, 1998, INT J MOL MED, V2, P685

[3] Human immunodeficiency virus resistance to AZT in MOLT4/8 cells is associated with a lack of AZT phosphorylation and is bypassed by AZT-monophosphate SATE prodrugs [J].

Cinatl, J ;

Groschel, B ;

Zehner, R ;

Cinatl, J ;

Perigaud, C ;

Gosselin, G ;

Imbach, JL ;

Doerr, HW .

ANTIVIRAL CHEMISTRY & CHEMOTHERAPY, 1997, 8 (04) :343-352

[4] VARIETY IN THE LEVEL OF GENE-CONTROL IN EUKARYOTIC CELLS [J].

DARNELL, JE .

NATURE, 1982, 297 (5865) :365-371

[5]

Eads CA, 1999, CANCER RES, V59, P2302

[6]

GAO WY, 1994, J BIOL CHEM, V269, P12633

[7] ddC- and 3TC-bis(SATE) monophosphate prodrugs overcome cellular resistance mechanisms to HIV-1 associated with cytidine kinase deficiency [J].

Gröschel, B ;

Himmel, N ;

Cinatl, J ;

Périgaud, C ;

Gosselin, G ;

Imbach, JL ;

Doerr, HW ;

Cinatl, J .

NUCLEOSIDES & NUCLEOTIDES, 1999, 18 (4-5) :921-926

[8] Effects of cycloSal-d4TMP derivatives in H9 cells with induced AZT resistance phenotype [J].

Gröschel, B ;

Meier, C ;

Zehner, R ;

Cinatl, J ;

Doerr, HW ;

Cinatl, J .

NUCLEOSIDES & NUCLEOTIDES, 1999, 18 (4-5) :933-936

[9] Viral and cellular factors for resistance against antiretroviral agents [J].

Gröschel, B ;

Cinatl, J ;

Cinatl, J .

INTERVIROLOGY, 1997, 40 (5-6) :400-407

[10] A controlled trial of two nucleoside analogues plus indinavir in persons with human immunodeficiency virus infection and CD4 cell counts of 200 per cubic millimeter or less [J].

Hammer, SM ;

Squires, KE ;

Hughes, MD ;

Grimes, JM ;

Demeter, LM ;

Currier, JS ;

Eron, JJ ;

Feinberg, JE ;

Balfour, HH ;

Dayton, LR ;

Chodakewitz, JA ;

Fischl, MA .

NEW ENGLAND JOURNAL OF MEDICINE, 1997, 337 (11) :725-733

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