S-phase specific

Costa M, Cantoni O, DeMars M, et al. 1982. Toxic metals produce S-phase-specific cell cycle block. Res Commun Chem Pathol Pharmacol 38 405-419. 

Cytarabine -antimetabolite which is S-phase specific during DNA... 

Gemcitabine - nucleoside analogue antimetabolite S-phase specific cytotoxicity -bone marrow suppression—most commonly thrombocytopenia -nausea and vomiting -fever during administration -elevated transaminases -rash... 

In addition to heterochromatic silencing, SUV39H1 H3 methyltransferase and HPl are involved in repression of euchromatic genes. The transcription factor E2F has a pivotal role in regulating the expression of S-phase-specific genes. Repression of these genes is through the retinoblastoma (Rb) protein which binds to E2F. 

Hennequin C, Giocanti N, Favaudon V. S-phase specificity of cell killing by docetaxel (Taxotere) in synchronised HeLa cells. BrJ Cancer 1995 71(6) 1194—1198. 

CPTs kill cells in S-phase by the mechanism involving the replication fork collision model. It is known that reversible TOPO-1 CPT DNA cleavable complexes are in themselves nonlethal and that collisions with an advancing replication fork cause cell death (8). Several biochemical events follow collision with the replication fork the formation of double-strand breaks, irreversible arrest of the replication fork, and the formation of TOPO-1-linked DNA break at the site of collision. These mechanisms account for the S-phase-specific cytotoxicity seen at relatively low doses of camptothecin. 

Administration by experienced physician only pts should be hospitalized for 1st course d/t risk for severe Rxn Uses G1 adenoma, liver, renal cancers colon pancreatic CAs Action Converted to 5-FU inhibits thymidylate synthase DNA synth (S-phase specific) Dose 0.1-0.6 mg/kg/d for 1-6 wk (per protocols) usually intra-arterial for liver mets Caution [D, -] Interaction w/ vaccines Contra BM... 

Fluorouracil/ Topical [5-FU] (Efudex) [Antineoplastic/ Antimetabollte] Uses Basal cell carcinoma actinic/solar k atosis Action Inhibits thymidylate S5mthetase (-1- DNA S5mth, S-phase specific) Dose 5% cream bid X 2-6 wk Caution [D, ] Irritant chemo Contra Component sensitivity Disp Cream, soln SE Rash, dry skin, photosens EMS See RuorouracU OD See RuorouracU... 

Some drugs that exert their maximum cytotoxicity during the S-phase of the cycle also prevent cells from progressing through the cell cycle to the S-phase this is accomplished by sublethal inhibition of RNA and protein synthesis. The antimetabolites methotrexate, fluo-rouracU, and mercaptopurine all can inhibit RNA synthesis in Gi- and Gz-phases and inhibit DNA synthesis during S-phase. This inhibition of cell cycle progression actually may result in reduced cytotoxicity, and such agents have been termed S-phase-specific but self-limited. 

Hydroxyurea (Hydrea) inhibits the enzyme ribonucleotide reductase and thus depletes intracellular pools of deoxyribonucleotides, resulting in a specific impairment of DNA synthesis. The drug therefore is an S-phase specific agent whose action results in an accumulation of cells in the late Gj- and early S-phases of the cell cycle. 

Cytarabine (ara-C) is an S phase-specific antimetabolite that is converted by deoxycytidine kinase to the 5 -mononucleotide (ara-CMP). Ara-CMP is further metabolized to the diphosphate and triphosphate metabolites, and the ara-CTP triphosphate is felt to be the main cytotoxic... 

In view of cytarabine s S phase specificity, the drug is highly schedule-dependent and must be given either by continuous infusion or every 8-12 hours for 5-7 days. Its activity is limited almost entirely to treatment of acute myelogenous leukemia, for which it is a major drug. Adverse effects are listed in Table 55-3. 

S-phase-specific drugs like adriamydn or M-phase-apedfic drugs like vincristine. it these possfoie hazards can be ruled out, a drug like PEu-I-aSP may represent a significant step ahead toward better tolerance of the enzyme. 

Gemcitabine is an S-phase-specific pyrimidine nucleoside analogue of deoxycytidine (2, 2 -difluorodeoxycytidine) that is structurally similar to cytosine arabinoside. It has been used to treat metastatic urothelial carcinoma of the bladder, pancreatic cancer, and some other solid tumors. 

Banik GG, Todd PW Kompala DS (1996) Foreign protein expression from S phase specific promoters in continuous cultures of recombinant CHO cells. Cytotech-nology 22 179-184. 

Bjorklund S, Skog S, Tribukait B, Thelander L (1990) S-phase-specific expression of mammalian ribonucleotide reductase R1 and R2 subunit mRNAs. Biochemistry 29 5452-5458... 

Lee TY, Lai TY, Lin SC et al (2010) The B56gamma3 regulatory subunit of protein phosphatase 2A (PP2A) regulates S phase-specific nuclear accumulation of PP2A and the G1 to S ttansition. J Biol Chem 285 21567-21580... 

Zidovudine is a synthetic thymidine analog with potent activity against a broad spectrum of retroviruses including HIV-1, HlV-2, and human T-ceU lymphotrophic viruses (HTLV) 1 and II. The drug has no impact in cells already infected with HIV. It is most effective in activated lymphocytes because the phosphorylating enzyme, thymidine kinase, is S-phase specific. 

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