Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: KEGG:D06369 (ZnCl2)
 1,308 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The ubiquitous, low-molecular-weight, thiol-rich, metal-binding protein, metallothionein (MT), can be induced in cultured normal human fibroblasts (NF) and xeroderma pigmentosum (XP) cells by exposure to ZnCl2. Both NF and XP cells tolerate up to 200 microM ZnCl2 in the growth medium, upon addition of ZnCl2 (200 microM) to monolayer cultures, both NF and XP cells showed similar kinetics for the induction of MT synthesis: Within 7 hours the MT synthesis rate rose from a low, marginally detectable rate to a maximal rate at least 50-fold greater than the basal rate. The induction of MT synthesis in both cell types was inhibited by actinomycin D (5 microgram/ml), indicating that the induction process is controlled at the level of transcription. Exposure of NF and XP cells to far ultraviolet light (UV) followed by induction with ZnCl2 resulted in a UV dose-dependent decrease in the he maximal rate of MT synthesis measured 8.5 hours postirradiation. The UV sensitivity of the MT induction was greater in XP cells than in NF cells. However, considerations of the differential repair capacities of NF and XP cells superimposed upon the kinetics of MT induction were invoked to explain the apparent differential UV sensitivity of MT induction. Liquid holding recovery experiments showed that NF cells possess the capacity to reactivate this inducible gene function rapidly while XP cells are deficient in the reactivation capacity. These results are discussed in the context of both UV transcriptional mapping of this inducible gene function and development of techniques for measuring repair of transcription-blocking lesions.
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PMID:Differential reactivation of zinc-mediated metallothionein induction in ultraviolet-irradiated normal and repair-deficient human cells. 706 76

Synthesis of the low molecular weight, thiol-rich, metal-binding metallothioneins (MTS) is undetectable in normal human (NF) or xeroderma pigmentosum (XP) fibroblasts grown in the absence of excess ZnCl2. Addition of 200 microM ZnCl2 to the growth medium produces an increased MT synthesis rising from the basal rate to a rate at least 50-fold greater than basal rate within 7 h. MT induction kinetics in confluent and in exponentially growing subconfluent monolayers were indistinguishable. Zn2+-mediated MT induction is sensitive to actinomycin D suggesting that the induction process is under transcriptional control. Ultraviolet light irradiation causes a dose-dependent inactivation of Zn2+-mediated MT induction in both NF and XP cells. Post-irradiation incubation of UV-irradiated cells using liquid holding techniques leads to reactivation of Zn2+-mediated MT induction in NF cells but not in XP cells. These findings suggest the utility of MT induction produce transcription-terminating lesions, and (b) in evaluating cellular repair capacity for this class of DNA lesions.
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PMID:Ultraviolet light inactivation of zinc-mediated metallothionein induction in normal and repair-deficient human cells. 712 93

2-Chloro-2'-deoxyadenosine (cladribine), an analog of deoxyadenosine, is an important new drug for the treatment of hairy cell leukemia and other forms of adult and pediatric leukemia. By a gel-shift binding assay, we identified an activity in HeLa nuclear extracts that recognizes and binds to oligonucleotides substituted with 2-chloroadenine (ClAde). The activity was specific for ClAde residues because control oligomers did not readily compete out the complex. The binding factor was a monomeric protein that was resistant to inactivation by heating at 45 degrees C but sensitive to heating at 65 degrees C, proteinase K treatment, and 5 mM ZnCl2. This protein, designated ClAde recognition protein (CARP), appeared to be related to a protein that recognized other forms of DNA damage. Gel-shift binding reactions with ultraviolet (UV)-irradiated oligomers revealed a UV-specific protein/DNA complex that had an electrophoretic mobility similar to that of the CARP/DNA complex, and CARP binding to ClAde-containing oligomers was readily competed out by UV-irradiated DNA. Moreover, CARP activity was present in extracts prepared from UV-sensitive xeroderma pigmentosum group A cells but not in a subset of cells from group E, suggesting that CARP was similar to a previously described repair associated factor, xeroderma pigmentosum-E binding factor. Our findings support a possible repair process for ClAde residues incorporated into cellular DNA.
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PMID:A human factor that recognizes DNA substituted with 2-chloroadenine, an antileukemic purine analog. 764 63