Cell-cycle delay

Results of methyl parathion assays involving effects on chromosomes have also been contradictory. For sister chromatid exchange, Waters et al. (1982) reported a positive response in Chinese hamster ovary cells only in the presence of metabolic activation system, while methyl parathion tested positive without a metabolic activation system in Chinese hamster V79 cells (Chen et al. 1981), cultured normal human lymphoid cells (Chen et al. 1981 Gomez-Arroyo et al. 1987 Sobti et al. 1982), and Burkitt s l5miphoma cells (Chen et al. 1981). Chen et al. (1981) found a significant dose-related increase in sister chromatid exchange in both hamster and human cultured cells, but dose-related cell cycle delays were less pronounced in human cell lines than in V79 cells. Negative results were obtained for chromosomal aberrations in human lymphocytes without a metabolic activation system (Kumar et al. 1993). 

Chen MM, Hsueh JE, Sirianni SR, et al. 1981. Induction of sister-chromatid exchanges and cell cycle delay in cultured mammalian cells treated with eight organophosphorus pesticides. Mutat Res 88 307-316. 

Singh S, Eehmann-Grube B, Boedde HW. 1984. Cytogenetic effects of paraoxon and methyl-parathion on cultured human lymphocytes SCE, clastogenic activity and cell cycle delay. Int Arch Occup Environ Health 54 195-200. 

The chromatid separation process has also remained mysterious. It is an autonomous process that does not direcdy depend on the mitotic spindle (Wilson 1925, Mazia 1961). This is most vividly seen in cells whose spindles have been destroyed by spindle poisons such as colchicine. In many organisms, in particular in plant cells, the cell cycle delay induced by colchicine is only transient and chromatids eventually split apart in the complete absence of a mitotic spindle (Mole-Bajer 1958, Rieder Palazzo 1992) (Fig. 2). Mitosis in the presence of colchicine or colcemid (known as c-mitosis) leads to the production of daughter cells with twice the normal complement of chromosomes. This process is routinely used for manipulating plant genomes and may contribute to the therapeutic effects of taxol in treating breast cancer. 

In a recent study, the antiproliferative effect of different carotenoids, including (3-carotene, lycopene and lutein, on PCNA and cyclin Dl expression in human KB cells have been studied. The results indicate that carotenoids suppressed cell growth by acting as inhibitors of the expressions of PCNA and cyclin Dl, although in a different extent (Cheng et al., 2007). On the other hand, (3-carotene was able to induce a cell cycle delay in G2/M phase by decreasing the expression of cyclin A in human colon adenocarcinoma cells (Palozza et al., 2002a). 

Chlordecone (1.67-10.00 mg/L) increased the frequency of sister chromatid exchange in CHO cells but only in the absence of S9 activation and only in the presence of cell-cycle delay the results were confirmed in a repeat trial (Galloway et al. 1987). By contrast, chlordecone alcohol was negative for sister chromatid exchange induction both with and without S9 activation (Galloway et al. 1987). Subcytotoxic doses of mirex did not induce unscheduled DNA synthesis in primary hepatocytes recovered from rats, mice, or hamsters (Maslansky and Williams 1981 Williams 1980). Similar results were obtained by Probst et al. (1981) using primary rat hepatocytes exposed to 1,000 pmol/L mirex. Chlordecone was also uniformly negative in unscheduled DNA synthesis assays of primary rat hepatocytes (Probst et al. 1981 Williams 1980). 

W. K. Lutz and A. Kopp-Schneider, Threshold dose response for tumor induction by genotoxic carcinogens modeled via cell-cycle delay. Toxicological Sciences, 1999,49(1), 110-115. 

A dose-related increase in genotoxicity is one of the relevant criteria for identification of positive findings. In practice, this will be most helpful for in vitro tests, but care is needed to check for cytotoxicity or cell cycle delay, which may cause deviations from a dose-response related effect in some experimental systems. 

Bohlke. J.U.. Singh. S. Goedde, H.W. (1983) Cytogenetic effects of acetaldehyde in lymphocytes of Germans and Japanese SCE, clastogenic activity, and cell cycle delay. Hum. Genet.. 63. 285-289... 

Ataxia telangiectasia (AT) ATM Cell cycle delay for repair of ds breaks... 

Conner et al. (1987) did not observe any effect on sister chromatid exchange in bone marrow, alveolar macrophages, and lymphocytes of mice exposed to MIC however, cell cycling of lymphocytes and bone marrow cells from mice exposed to >15 ppm MIC was almost completely suppressed. On the other hand, MIC was found to be genotoxic in rats (Dutta et al, 1988) and caused dose-related increases in sister chromatid exchange as well as chromosomal aberrations in hamster ovary cells in addition to cell cycle delay in mice (Shelby et al, 1987). MIC has also been... 

Cellular processes that can protect DNA integrity once a DNA lesion has occurred are well-characterized. Broadly, these responses can be categorized as DNA repair, cell-cycle delay, apoptosis (i.e., programmed cell dealh), and cellular differentiation... 

Maity, A., McKenna, W. G., 8c Muschel, R. J. (1994). The molecular basis for cell cycle delays following ionizing radiation A review. Radiotherapy Oncology, 31, 1—13. 

Fig. 14.4a-c. Radiation-induced cell cycle delays in irradiated mammalian cells, a Delay in Gl, as detected in the normal human fibroblast strain HHNF irradiated with 3.5 Gy. Confluent cells were stimulated into the cell cycle, and proliferating cells were identified by BrdU incorporation, which was followed by antibody staining and analysis by flow cytometry (kindly provided by Dr. Ingo Brammer, Laboratory of Radiobiology Experimental Radiation Oncology, University Medical Center... 

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