Cytotoxicity marked

The effect of variability on drug cytotoxicity markedly depends on the temporal pattern of 5-FU delivery. When the peak in the circadian delivery of 5-FU occurs at 4 p.m., i.e. when the circadian schedule of 5-FU administration is most toxic to the cells, whether in the absence or presence of entrainment by the circadian clock, cytotoxicity increases as the degree of variability decreases. The effect is more marked in the conditions of entrainment a threshold in cytotoxicity then exists between... 

Amino-5-iodo-2, 5 -dideoxyuridine [56045-73-9] (13) C2H22IN2O4, was synthesized ia 1975 (27) and was found effective against herpes keratitis ia rabbits (28). This compound is markedly less cytotoxic than IdU, iadicating that it may have a safer and more specific mode of antiviral activity. A potential limitation of this group of nucleosides is their specificity, for they fail to inhibit all strains of herpes vimses. The specific antiviral activity of (13) is considered to be a result of the incorporation of the 5 -Ai-phosphate into both viral and host DNA in infected cells, but not into the DNA of normal cells. Phosphorylation of (13) occurs only in herpes vims-infected cells, brought about by a vims-induced thymidine kinase (29). 

Further experiments focused therefore on [RuCl(en)(r 6-tha)]+ (12) and [RuCl(rj6-p-cym)(en)]+ (22), which represent the two different classes, and their conformational distortion of short oligonucleotide duplexes. Chemical probes demonstrated that the induced distortion extended over at least seven base pairs for [RuCl(rj6-p-cym)(en)]+ (22), whereas the distortion was less extensive for [RuCl(en)(rj6-tha)]+ (12). Isothermal titration calorimetry also showed that the thermodynamic destabilization of the duplex was more pronounced for [RuCl(r 6-p-cym)(en)]+ (22) (89). DNA polymerization was markedly more strongly inhibited by the monofunctional Ru(II) adducts than by monofunctional Pt(II) compounds. The lack of recognition of the DNA monofunctional adducts by HMGB1, an interaction that shields cisplatin-DNA adducts from repair, points to a different mechanism of antitumor activity for the ruthenium-arenes. DNA repair activity by a repair-proficient HeLa cell-free extract (CFE) showed a considerably lower level of damage-induced DNA repair synthesis (about six times) for [RuCl(en)(rj6-tha)] + compared to cisplatin. This enhanced persistence of the adduct is consistent with the higher cytotoxicity of this compound (89). 

The answer is c. (Hardman, pp 649—650.) Acute hyperuricemia, which often occurs in patients who are treated with cytotoxic drugs for neoplasic disorders, can lead to the deposition of urate crystals in the kidneys and their collecting ducts. This can produce partial or complete obstruction of the collecting ducts, renal pelvis, or ureter. Allopurinol and its primary metabolite, alloxanthine, are inhibitors of xanthine oxidase, an enzyme that catalyzes the oxidation of hypo xanthine and xanthine to uric acid. The use of allopurinol in patients at risk can markedly reduce the likelihood that they will develop acute uric acid nephropathy. 

Contrary to the findings in BN rats, in Lewis rats [202] mercuric chloride induces immunosuppression, the number of suppressor/cytotoxic cells increase in the spleen and lymph nodes, an inhibition occurs of T cell responsiveness to mitogens and alloantigens and there is a marked reduction of the local graft versus host reaction. 

The cytotoxicity of Au(I) complexes is markedly dependent on the ligands. A large number of Au(I) phosphine complexes are toxic to cells in the micromolar concentration range. For example, some linear Au(I) phosphine complexes, including the antiarthritic complex aura-nofin (see Section VII), are potently cytotoxic toward cancer cells in culture (189). 

Cell suspensions of exponentially growing cells are prepared as in the cytotoxicity assay, except that 6 ml of media required for each treatment culture contains 107 cells (3-h treatment) or 3 x 106 cells (more than 3 h treatment). The number of cells per treatment may be increased if marked cytotoxicity is expected, to allow enough cells to survive (e.g., if 20% survival or less is expected, 2 x 107 cells may be treated). 

Our previous studies showed that CNTs exhibit marked cytotoxicity (Cui et al., 2005 Tian et al., 2006). For example, SWCNTs can inhibit HEK293 cell proliferation, decrease cell adhesive ability in a dose-and time-dependent manner as shown in Fig. 9.7. HEK293 cells also exhibit active responses to SWCNTs such as secretion of some 20-30 kd proteins to wrap SWCNTs, aggregation of cells attached by SWCNTs and formation of nodular structures as shown in Fig. 9.8. Cell cycle analysis showed that 25pg/ml SWCNTs in medium induced Gt arrest and cell apoptosis in HEK293 cells as shown in Fig. 9.9. Biochip analysis showed that SWCNTs can induce up-regulation expression of cell cycle-associated genes such... 

Cyclo(Met-Tyr) and cyclo(Met-Trp) produced a marked inhibitory effect toward platelet adhesion induced by both ADP and thrombin. A moderate cytotoxic effect was displayed by cyclo(Met-Trp) against HeLa (55.85% inhibition), HT-29 (39.80% inhibition), and MCF-7 cancer cells (54.96% inhibition) whereas... 

The proliferation of cytotoxic T-cells is markedly impaired upon infection with a newly discovered human immunodeficiency virus, designated HIV-V. The defect has been traced to the expression of a viral-encoded enzyme that inactivates a host-ceU nuclear protein required for DNA replication. Which protein is a potential substrate for the viral enzyme ... 

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