Kinetics cell-cycle

In summary, genotoxicity studies of endosulfan have provided evidence that this compound is mutagenic and clastogenic, and that it induces effects on cell cycle kinetics in two different mammalian species. However, some of these data may be suspect because some formulations of endosulfan have contained epichlorohydrin, a known genotoxic chemical, as a stabilizer (Hoechst 1990). It should be noted that humans may also be exposed to epichlorohydrin along with endosulfan. 

Terry NH, White RA. Cell cycle kinetics estimated by analysis of bromodeoxyuridine incorporation. Methods Cell Biol. 2001 63 355-74. 

Gong J, Traganos F, Darzynkiewicz Z. 1993. Simultaneous analysis of cell cycle kinetics at two different DNA ploidy levels based on DNA content and cyclin B measurements. 

Equivocal results have been found in geno-toxic assays, but endosulfan was mutagenic and clastogenic and induced effects on cell cycle kinetics in various in vivo and in vitro tests. ... 

Huang SM, Harari PM. Modulation of radiation response after epidermal growth factor receptor blockade in squamous cell carcinomas inhibition of damage repair, cell cycle kinetics, and tumor angiogenesis. Clin Cancer Res 2000 6 2166-2174. 

ROLE OF CELL CYCLE KINETICS ANTICANCER EFFECT... 

Information on cell and population kinetics of cancer cells explains, in part, the limited effectiveness of most available anticancer drugs. A schematic summary of cell cycle kinetics is presented in Figure 54-2. This information is relevant to the mode of action, indications, and scheduling of cell cycle-specific (CCS) and cell cycle-nonspecific (CCNS) drugs. Agents falling into these two major classes are summarized in Table 54-1. 

Morimoto, K. Wolff, S. (1980) Cell cycle kinetics in human lymphocyte cultures. Nature, 288, 604-606... 

The effects of elevated lactic acid concentration on the cell cycle kinetics of hybridoma cell growth and antibody production in batch culture were studied by Kromenaker and Srienc (1994). When 33 mM lactic acid was initially present, the specific growth rate was reduced by 37% and the cell-specific antibody production rate increased by a factor of 2.6 relative to a control culture with no additional lactic acid. 

Further information on cell cycle kinetics can be found in Cleaver (1967) and in Aheme et al. (1977). 

Irons RD, Heck Hd A, Moore BJ, et al. 1979. Effects of short-term benzene administration on bone marrow cell cycle kinetics in the rat. Toxicol Appl Pharmacol 51 399-409. 

A study that investigated the effects of uranyl nitrate hexahydrate on viability, cell cycle kinetics, micronuclei, chromosomal aberrations, and sister-chromatid exchanges in Chinese hamster ovary cells found an increased frequency of micronuclei, sister-chromatid exchanges, and chromosomal aberrations leading to the conclusion that uranyl nitrate hexahydrate was genotoxic under the conditions of the assay (Lin et al. 1993). 

Fig. 5. Cell cycle kinetics in normal and psoriatic germinative cells. This schematic diagram of the cell cycle is made to illustrate the relative times taken for a psoriatic and normal germinative cell to divide, and the proportions in the 2 cycles are accurate with respect to a time scale of 12 hours for the distance shown on the scale at the right. C.C. = total cell cycle time. The other periods of the cycle are labeled in the figure. The great difference between psoriatic and normal cells, especially in the time spent in Gi (interphase, or post mitotic period), can be appreciated. (We are indebted to Dr. G. Weinstein and Dr. P. Frost for preparing and allowing the use of this illustration.)...

B5. Bezwoda, W. R., and Meyer, K., Effect of alpha-interferon, 17 beta estradiol, and tamoxifen on estrogen receptor concentration and cell cycle kinetics of MCF7 cells. Cancer Res. 50(17), 5387-5391 (1990). 

Studies using single cells allow precise control of the extracellular environment and, therefore, can provide useful information on the cellular uptake of drugs and cell cycle kinetics during various types of treatment. Such detailed information cannot be obtained directly from whole-tissue (e.g., solid-tumor) studies because of the heterogeneous nature of tumor blood flow and vascular structure, and a variety of host factors. However, caution must be exercised in extrapolating the information obtained from single cells to the solid tumor in vivo. 

Describe the relevance of cell cycle kinetics to the modes of action and clinical uses of anticancer dmgs. 

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