A nonsense mutation (UAG) in the thymidine kinase gene of herpes simplex virus type 1 can be suppressed in vivo to produce active thymidine kinase by prior infection with a defective simian virus 40 stock which acts as a vector to introduce a functional suppressor tRNA gene into mammalian cells in culture. The suppression is specific for UAG, but not UGA or missense, mutants and restores thymid...

Thymidine kinase (TK) activity was examined in extracts of TK-deficient cells infected with low passage isolates of herpes simplex virus type 1 (HSV-1) obtained from patients with herpetic keratitis. TK activity induced by the virus, relative phosphorylation rates of thymidine and iododeoxyuridine (IUDR), and Km values for thymidine and for IUDR were compared for TK induced by the different vir...

Chick-mouse heterokaryons were obtained by UV-Sendai virus-induced fusion of chick erythrocytes with thymidine (dT) kinase-deficient mouse fibroblast [LM(TK(-))] cells. Autoradiographic studies demonstrated that 1 day after fusion, [(3)H]dT was incorporated into both red blood cell and LM(TK(-)) nuclei of 23% of the heterokaryons. Self-fused LM(TK(-)) cells failed to incorporate [(3)H]dT into n...

The cell line LM(TK(-)) Cl 1D, a derivative of mouse L fibroblasts deficient in thymidine kinase (EC 2.7.1.21) that shows very little thymidine kinase activity in extracts of whole cells as compared to the parental line, and that does not incorporate thymidine or 5-bromodeoxyuridine into nuclear DNA, has maintained the capacity to incorporate these precursors into mitochondrial DNA at a substan...

Perturbing deoxyribonucleoside triphosphate (dNTP) metabolism with inhibitors of the de novo synthesis of dNTP causes apoptosis in the interleukin-3 (IL-3)-dependent pre-B cell line BAF3. Under these conditions apoptosis is prevented when deoxyribonucleosides for dNTP synthesis are supplied in the culture medium. On the other hand, removal of IL-3 from cultures of BAF3 cells resulted in down-re...

Several new nucleosides with an oxetanosyl-N-glycoside group, named oxetanocins, were evaluated for their antiviral activities against varicella-zoster virus (VZV) in human embryo lung cells. 9-(2-deoxy-2-hydroxy-methyl-beta-D-erythro-oxetanosyl)guanine (OXT-G) and 9-(2-deoxy-2-hydroxymethyl-beta-D-erythro-oxetanosyl)-2- aminoadenine were effective against not only thymidine kinase-positive (TK...

Background: The organochlorine DDT has estrogenic activity but the mechanism underlying the estrogenic activity of this pesticide remains unclear. In the present investigation here, we studied the transcriptional effects of a synthetic organochlorine pesticide o,p’-DDT [1.1.1.-trichloro-2-(o-chlorophenyl)-2-p-chloriphenyl ethane] and its metabolite p,p'-DDE (2-2-bis(4/chlorophenyl)-1-1-di...

The expression of cytosolic human thymidine kinase (TK) occurs in a cell cycle-dependent manner. Here, we show that TK is hyperphosphorylated during the M phase in several human cell lines. Our data from characterizing TK phosphorylation in proliferating and M phase-arrested HeLa cells suggest that the polypeptide of TK is differentially phosphorylated during the progression of the cell cycle. ...

The broad substrate specificity of herpes simplex virus type 1 (HSV-1) thymidine kinase (TK) has provided the basis for selective antiherpetic therapy and, more recently, suicide gene therapy for the treatment of cancer. We have now constructed an HSV-1 TK mutant enzyme, in which an asparagine (N) residue is substituted for glutamine (Q) at position 125, and have evaluated the effect of this am...

Infections of Herpes simplex virus type 1 (HSV1) are associated with oral-facial infections, skin infections, and genital infections. During the past decade, potent agents against herpes virus infections have been found. The action of these agents is based on the difference between viral thymidine kinase (TK) and human TK. Thymidine kinase (TK, EC 2.7.1.21) is the key enzyme in the pyrimidine s...