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Proliferation Kinetics (proliferation + kinetics)
Selected AbstractsCell cycle effects resulting from inhibition of hepatocyte growth factor and its receptor c-Met in regenerating rat livers by RNA interference,HEPATOLOGY, Issue 6 2007Shirish Paranjpe Hepatocyte growth factor (HGF) and its receptor c-Met are involved in liver regeneration. The role of HGF and c-Met in liver regeneration in rat following two-thirds partial hepatectomy (PHx) was investigated using RNA interference to silence HGF and c-Met in separate experiments. A mixture of 2 c-Met-specific short hairpin RNA (ShRNA) sequences, ShM1 and ShM2, and 3 HGF-specific ShRNA, ShH1, ShH3, and ShH4, were complexed with linear polyethylenimine. Rats were injected with the ShRNA/PEI complex 24 hours before and at the time of PHx. A mismatch and a scrambled ShRNA served as negative controls. ShRNA treatment resulted in suppression of c-Met and HGF mRNA and protein compared with that in controls. The regenerative response was assessed by PCNA, mitotic index, and BrdU labeling. Treatment with the ShHGF mixture resulted in moderate suppression of hepatocyte proliferation. Immunohistochemical analysis revealed severe suppression of incorporation of BrdU and complete absence of mitosis in rats treated with ShMet 24 hours after PHx compared with that in controls. Gene array analyses indicated abnormal expression patterns in many cell-cycle- and apoptosis-related genes. The active form of caspase 3 was seen to increase in ShMet-treated rats. The TUNEL assay indicated a slight increase in apoptosis in ShMet-treated rats compared with that in controls. Conclusion: The data indicated that in vivo silencing of c-Met and HGF mRNA by RNA interference in normal rats results in suppression of mRNA and protein, which had a measurable effect on proliferation kinetics associated with liver regeneration. (HEPATOLOGY 2007.) [source] Intraperitoneal injection of d- galactosamine provides a potent cell proliferation stimulus for the detection of initiation activities of chemicals in rat liverJOURNAL OF APPLIED TOXICOLOGY, Issue 6 2005Yoshiji Asaoka Abstract In an in vivo 5-week initiation assay model, chemical hepatectomy by hepatotoxicant administration was utilized as a cell proliferation stimulus as an alternative to the two-thirds partial hepatectomy. The study investigated the effect of an intraperitoneal (i.p.) injection of d- galactosamine (d -gal) for this purpose in a medium-term liver bioassay, with a further focus on cell proliferation kinetics and cytochrome P450 (CYP) expression. In experiment I, cell proliferation in rat liver after a single administration of d -gal (700 mg kg,1, i.p.) was analysed by the bromodeoxyuridine (BrdU) labeling method, and CYP isozymes were quantified by immunoblotting. In experiment II, the induction of glutathione S-transferase placental form (GST-P) positive foci by 1,2-dimethylhydrazine (DMH) was evaluated in a modified in vivo 5-week initiation assay model. At 84 hours after single administration of d -gal (i.p.) the BrdU index was markedly elevated (27.5% ± 9.5%). Although CYP 2E1 and 1A2 apoprotein contents decreased transiently to less than 20% of the control level, subsequently they recovered to 60% and 40% of the control level, respectively, at 84 hours. Induction of GST-P positive foci in the group given DMH at 84 hours after a single administration of d -gal was significantly greater than in the control group, correlating with the kinetics of cell proliferation. In conclusion, the sensitivity of the present initiation assay using d -gal i.p. is high, so that d -gal i.p. can be considered an effective cell proliferation stimulus. Copyright © 2005 John Wiley & Sons, Ltd. [source] Cytogenetic damage in human lymphocytes following GMSK phase modulated microwave exposureBIOELECTROMAGNETICS, Issue 1 2002Guglielmo d'Ambrosio Abstract The present study investigated, using in vitro experiments on human lymphocytes, whether exposure to a microwave frequency used for mobile communication, either unmodulated or in presence of phase only modulation, can cause modification of cell proliferation kinetics and/or genotoxic effects, by evaluating the cytokinesis block proliferation index and the micronucleus frequency. In the GSM 1800 mobile communication systems the field is both phase (Gaussian minimum shift keying, GMSK) and amplitude (time domain multiple access, TDMA) modulated. The present study investigated only the effects of phase modulation, and no amplitude modulation was applied. Human peripheral blood cultures were exposed to 1.748 GHz, either continuous wave (CW) or phase only modulated wave (GMSK), for 15 min. The maximum specific absorption rate (,5 W/kg) was higher than that occurring in the head of mobile phone users; however, no changes were found in cell proliferation kinetics after exposure to either CW or GMSK fields. As far as genotoxicity is concerned, the micronucleus frequency result was not affected by CW exposure; however, a statistically significant micronucleus effect was found following exposure to phase modulated field. These results would suggest a genotoxic power of the phase modulation per se. Bioelectromagnetics 23:7,13, 2002. © 2002 Wiley-Liss, Inc. [source] Differential Effects of Partial Hepatectomy and Carbon Tetrachloride Administration on Induction of Liver Cell Foci in a Model for Detection of Initiation ActivityCANCER SCIENCE, Issue 10 2001Hiroki Sakai Differential effects of partial hepatectomy (PH) and carbon tetrachloride (CC14) administration on induction of glutathione S-transferase placental form (GST-P)-positive foci were investigated in a model for detection of initiation activity. Firstly, we surveyed cell proliferation kinetics and fluctuation in cytochrome P450 (CYP) mRNA levels by means of relative-quantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR) and CYP 2E1 apoprotein amount by immuno-blotting (experiment I) after PH or CC14 administration. Next, to assess the interrelationships among cell proliferation, fluctuation of CYPs after PH or CC14 administration and induction of liver cell foci, the non-hepatocarcinogen, 1,2-dimethylhydrazine (DMH) was administered to 7-week-old male F344 rats and initiated populations were selected using the resistant hepatocyte model (experiment II). In experiment I, the values of all CYP isozyme mRNAs after PH or CC14 administration were drastically decreased at the 12-h tune point. From 72 h, mRNAs for all CYP isozymes began increasing, with complete recovery after 7 days. The CYP 2E1 apoprotein content in the PH group fluctuated weakly, whereas in the CC14 group it had decreased rapidly after 12 h and was still low at the 48 h point. In experiment II, induction of GST-P-positive foci was related to cell kinetics in the PH group, with about a 6-h time lag between tune for carcinogen administration giving greatest induction of GST-P-positive foci and peaks in bromodeoxyuridine (BrdU) labeling, presumably due to the necessity for bioactivation of DMH. With CC14 administration, induction of foci appeared dependent on the recovery of CYP 2E1. In conclusion, PH was able to induce cell proliferation with maintenance of CYP 2E1, therefore being advantageous for induction of liver cell foci in models to detect initiation activity. [source] | ||||||||||