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J K Chen

Publications and source records attributed to J K Chen.

At least 37 records · Page 2Linked to original sources
PubMed2000

Promotive effect of diethylstilbestrol on urethan-induced mouse lung tumorigenesis.

The effect of diethylstilbestrol (DES) on urethan-induced mouse lung tumorigenesis was assessed by a single intraperitoneal injecting of urethan (50 mg/kg) or/and multi intramuscular injecting of DES (5 or 50 mg/kg). All mice were sacrificed 18 weeks after administration, and the lung tumors were examined histopathologically. DES did not produce an elevated lung tumor response when administered alone, but it produced a statistically significant enhancement of incidence of tumors, average number of tumors, incidence of cancers and constituent ratio of malignant tumors when given in conjunction with urethan. The results indicated that DES may be a promoter in lung tumor formation.

Animals↗
PubMed2000

The USF proteins regulate transcription of the follicle-stimulating hormone receptor but are insufficient for cell-specific expression.

Expression of the FSH receptor (FSHR) is limited to granulosa cells of the ovary and Sertoli cells of the testis. Previous studies showed that an E box in the proximal promoter of the FSHR gene is required for transcription and that the predominant E box binding proteins are the ubiquitous transcription factors, upstream stimulatory factor 1 (USF1) and USF2. Through cotransfection analysis, we have shown that both wild-type and dominant negative forms of the USF proteins regulate the rat FSHR promoter and that transcriptional activation of FSHR required several domains within the amino-terminal portion of the USF proteins. Analysis of the FSHR promoter region using in vivo genomic footprinting indicated that the E box is occupied by proteins in Sertoli cells but not in cells that fail to express the receptor, despite the presence of the USF proteins. To help delineate the regions of the rat FSHR gene required for correct spatial and temporal expression, transgenic mice harboring two constructs containing variable amounts of 5'-flanking sequence (5,000 bp and 100 bp) were generated. Examination of 16 different transgenic lines revealed varied transgene expression profiles with multiple lines having different amounts of ectopic expression and two lines failing to express the transgene. In addition, little or no expression was observed in Sertoli cells. These studies indicate that additional regulatory sequences outside the region from -5,000 to +123 bp are needed for proper expression in Sertoli cells.

Animals↗
PubMed2000

Biological effects of cementum and bone extracts on human periodontal fibroblasts.

BACKGROUND: Non-collagenous proteins of mineralized tissues play important roles in bone induction during mineralization and in regulating the activity of many types of mesenchymal cells. This study was conducted to determine the effects of acetic acid extracts of bone and cementum on alkaline phosphatase (ALPase) activity and in vitro mineralization of cultured human periodontal fibroblasts (hPF). METHODS: Alveolar bone and cementum obtained from clinically healthy subjects were extracted by a solution containing 0.5 M acetic acid and enzyme inhibitors. Osteoblastic phenotypes of hPF were assayed by ALPase activity, gene expression of bone marker proteins, and the ability to produce in vitro mineralization in culture media containing 50 microg/ml ascorbic acid, 10 mM sodium beta-glycerophosphate, and 10(-7) M dexamethasone. The effects of cementum and bone extracts on the expression of osteoblastic phenotypes in hPF were also determined. RESULTS: Many protein components, varying in molecular weight from 10 to 14 to 120 kDa, were detectable in 10% SDS-PAGE of both cementum and alveolar bone extracts. The hPF cells were found to exhibit a moderate ALPase activity when compared with rat osteosarcoma (ROS) 17/2.8 cells under the same experimental conditions. Gene expression for ALPase, osteocalcin bone sialoprotein, osteopontin, and BMP-7 at mRNA message was detected by RT-PCR in hPF and ROS 17/2.8 cells. The confluent hPF and ROS 17/2.8 cells showed evidence of calcium deposition in the extracellular milieu at 30 and 15 to 30 days' cultures, respectively, under a mineralization medium. The hPF appeared to form mineralized foci with morphological characteristics different from the mineralized nodules produced by ROS 17/2.8 cells. The addition of low concentrations (5 microg/ml) of either cementum or bone extract produced an increase in the size and number of mineralization spots, as well as greater ALPase activity in both hPF and ROS 17/2.8 cultures during the observation periods. CONCLUSIONS: These results suggest that hPF possess certain mineralizing phenotypes, and that acetic acid extracts of bone and cementum contain components capable of stimulating osteogenic differentiation of hPF.

Acetic Acid↗
PubMed2000

Effect of exercise training on oxidized LDL-mediated platelet function in rats.

This study investigates how exercise training affects Oxidized LDL (Ox-LDL) mediated-platelet activation. Five-week-old male Wistar rats were assigned to either control or trained groups. Trained rats were treadmill-trained for 10 weeks after familiarization. The following measurements were taken in both control and trained groups: Ox-LDL-mediated platelet aggregability and [Ca2+]i, plasma and platelet-derived nitric oxide (NO) metabolite (nitrite plus nitrate) levels, and antiaggregating activity of NO derived from endothelial cells. Based on those measurements, major findings in this study can be summarized as follows: 1) the trained group had a higher plasma -NO metabolite level than the control group; 2) the trained group had a lower platelet aggregability and [Ca2+]i elevation and a higher platelet derived-NO metabolite level than the control group; 3) the trained group had lower Ox-LDL-potentiated platelet aggregability and [Ca2+]i elevation and Ox-LDL-attenuated NO metabolite in platelet than the control group; 4) treating the platelet with L-arginine inhibited Ox-LDL-potentiated platelet activation in both control and trained groups; 5) Ox-LDL enhances platelet aggregation directly although impairing NO bioactivity but not guanylate cyclase activity in both control and trained groups. Results in this study demonstrate that exercise training decreases Ox-LDL-potentiated platelet activation most likely by enhancing platelet-derived NO release.

Adenosine Diphosphate↗
PubMed2000

Effect of strenuous arm exercise on oxidized-LDL-potentiated platelet activation in individuals with spinal cord injury.

This study investigates how strenuous arm exercise affects oxidized-low density lipoprotein (O(X)-LDL) mediated-platelet activation in patients with SCI. Ten patients with SCI and ten age- and sex-matched healthy subjects exercised strenuously using an arm crank ergometer. The following measurements were taken both when the subjects were at rest, and immediately after exercise: plasma lipid profile, O(X)-LDL mediated platelet aggregability and [Ca(2+)]i, urinary 11-dehydro-thromboxane B2 (11-dehydro-TXB2) and 8-iso-prostaglandin F(2alpha), (8-iso-PG F(2alpha)) contents, and plasma NO metabolite (nitrite plus nitrate) level. Based on these measurements, the major findings of this study can be summarized as follows: 1) the SCI group had higher urinary 8-iso-PGF(2alpha) and 11-dehydro-TXB2 contents, but a lower plasma nitrite plus nitrate level than the control group; 2) at rest, the SCI group had a higher platelet aggregability and [Ca(2+)]i, and O(X)-LDL-potentiated platelet activation than the control group; 3) O(X)-LDL-potentiated platelet aggregation was enhanced by strenuous arm exercise in both groups, but the effect of exercise was more pronounced in the SCI group than in the control group; 4) treating the platelet with L-arginine inhibited O(X)-LDL-potentiated platelet activation in both groups. The study concludes that individuals with SCI had more extensive resting and exercise-enhanced O(X)-LDL-potentiated platelet activation and greater amounts of preformed lipid peroxides than those without SCI. Therefore, supplementation therapy with antioxidants may be needed for patients with SCI, especially in a strenuous arm exercise period.

Adult↗
PubMed2000

[Effect of interleukin 2 on the expression of estrogen receptors in the anterior pituitary of rats].

Using primary serum-free cell culture combined with immunocytochemistry and semi-quantified RT-PCR methods, we observe the modulation of estrogen receptor alpha (ERalpha) and beta (ERbeta) by interleukin-2 (IL-2) in rat anterior pituitary. The results show that IL-2 up-regulates the level of ERalpha protein and the expression of ERalpha mRNA, but down-regulates those of ERbeta. The density per cell of ERalpha-immunoreactive (ir) cells increases from 48.740 4.567 to 81.188+/-6.619, whereas that of ERbeta -ir cells decreases from 102.560+/-6.250 to 72.718+/-7.623 after rhIL-2 (10 microgram/L) incubation for 48 h. In parallel with these changes, the ratio of ERalpha/ beta -actin mRNA increases from 0.1511 to 0.4334, and ERbeta /beta -actin mRNA declines from 0.3822 to 0.1528. It is likely that IL-2 has direct regulatory effect on ER in anterior pituitary.

Animals↗
PubMed2000

[Interleukin-2 stimulates the proliferation of cultured RC-4B/C pituitary adenoma cell line].

The aim of the present study was to investigate whether interleukin-2 (IL-2) is involved in the proliferation control of the cultured RC-4B/C cell, which is a derived pituitary adenoma cell line of the rat. The level of cell proliferation was estimated by assessing (3)H-thymidine ((3)H-TdR) incorporation rate. IL-2 (10 1000 U/ml) significantly stimulated (3)H-TdR incorporation into the cell line in a dose-dependent manner. Specific PTK inhibitor tyrphostin (1 micromol/L) suppressed RC-4B/C cell proliferation and blocked the effect of IL-2 on RC-4B/C cells. After the PKA signaling pathway was inhibited by specific PKA inhibitor H-9 (1 micromol/L), the proliferation rate of RC-4B/C cells increased significantly. H-9 also enhanced the stimulation of IL-2 on RC-4B/C cell growth. Anti-estrogen tamoxifen (1 micromol/L) had no significant effect on the action of IL-2 on the proliferation of RC-4B/C cells. In conclusion, it is suggested that IL-2 modulates the proliferation of the cultured RC-4B/C pituitary adenoma cell line, and the action is closely related with the PTK and PKA signaling pathway.

Adenoma↗
PubMed1999

Transfection of an active cytochrome P450 arachidonic acid epoxygenase indicates that 14,15-epoxyeicosatrienoic acid functions as an intracellular second messenger in response to epidermal growth factor.

A common feature of most isolated cell systems is low or undetectable levels of bioactive cytochrome P450. We therefore developed stable transfectants of the renal epithelial cell line, LLCPKcl4, that expressed an active regio- and enantioselective arachidonic acid (AA) epoxygenase. Site-specific mutagenesis was used to convert bacterial P450 BM-3 into an active regio- and stereoselective 14S,15R-epoxygenase (F87V BM-3). In clones expressing F87V BM-3 (F87V BM-3 cells), exogenous AA induced significant 14S,15R-epoxyeicosatrienoic acid (EET) production (241. 82 ng/10(8) cells, >97% of total EETs), whereas no detectable EETs were seen in cells transfected with vector alone. In F87V BM-3 cells, AA stimulated [3H]thymidine incorporation and increased cell proliferation, which was blocked by the tyrosine kinase inhibitor, genistein, by the phosphatidylinositol 3 (PI-3) kinase inhibitors, wortmannin and LY294002, and by the mitogen-activated protein kinase kinase inhibitor, PD98059. AA also induced tyrosine phosphorylation of extracellular signal-regulated kinase (ERK) and PI-3 kinase that was inhibited by the cytochrome P450 BM-3 inhibitor, 17-ODYA. Epidermal growth factor (EGF) increased EET production in F87V BM-3 cells, which was completely abolished by pretreatment with either 17-ODYA or the phospholipase A2 (PLA2) inhibitor, quinacrine. Compared with vector-transfected cells, F87 BM-3 transfected cells demonstrated marked increases in both the extent and sensitivity of DNA synthesis in response to EGF. These changes occurred in the absence of significant differences in EGF receptor expression. As seen with exogenous AA, EGF increased ERK tyrosine phosphorylation to a significantly greater extent in F87V BM-3 cells than in vector-transfected cells. Furthermore, in these control cells, neither 17-ODYA nor quinacrine inhibited EGF-induced ERK tyrosine phosphorylation. On the other hand, in F87V BM-3 cells, both inhibitors reduced ERK tyrosine phosphorylation to levels indistinguishable from that seen in cells transfected with vector alone. These studies provide the first unequivocal evidence for a role for the AA epoxygenase pathway and endogenous EET synthesis in EGF-mediated signaling and mitogenesis and provide compelling evidence for the PLA2-AA-EET pathway as an important intracellular-signaling pathway in cells expressing high levels of cytochrome P450 epoxygenase.

8,11,14-Eicosatrienoic Acid↗
PubMed1999

Immunolocalization of high-density lipoproteins in arterial walls of rats.

The inverse correlation between serum high-density lipoprotein (HDL) levels and coronary heart disease in humans suggests that HDL has a protective effect against the development of atherosclerosis. However, there is a lack of data concerning its distribution across the arterial wall. In order to detect this lipoprotein, we performed immunogold labeling on ultrathin sections of L.R. White embedded rat arterial tissue. Electron microscopic examination revealed that HDL was localized in the cytoplasm of the endothelial cells and the smooth muscle cells, but not in the nucleus or other organelles. The HDL was also present in the subendothelial space, the extracellular matrix as well as the intercellular clefts between the endothelial cells. Quantitative study revealed that rats on a high cholesterol diet for one month have more immunogold labeling (P < 0.05) in the subendothelial space, the smooth muscle cells and the extracellular matrix as compared to rats on a normal diet. After 12 months of normal diet, the intracellular labeling was significantly increased (P < 0.05) in the endothelial cells and the smooth muscle cells as compared to 1 month on the normal diet. The increase was greater (P < 0.05) for the high-cholesterol diet than for the normal diet treatment.

Animals↗
PubMed1999

Tuberculin purified protein derivative up-regulates the telomerase activity of peripheral blood mononuclear cells from patients with pulmonary tuberculosis.

Telomerase activity was detectable in cells of tuberculous pleural effusions at high percentage. To investigate the possible role of telomerase in the immune function, we examined the proliferating state and the expression of telomerase activity in peripheral blood mononuclear cells (PBMC) from 13 patients with pulmonary tuberculosis (TB) and 13 healthy volunteers in response to tuberculin purified protein derivative (PPD) challenge. Exposure of cells to phytohemagglutinin (PHA) significantly promoted PBMC proliferation during a 6 day-period in both TB patient and healthy volunteer groups. PPD treatment also significantly promoted PBMC proliferation during a 6 day-period in TB patient group, but had no significant effect in healthy volunteer group. During the same period, telomerase activity was detected in every PHA- and PPD-treated samples of the TB patient group. However, the telomerase activity was not detected in PPD-treated samples from healthy donors and all the untreated samples. Our results indicate that the telomerase activity in PBMC could be induced by PPD stimulation in TB patients. Telomerase activity may thus play a permissive role in cell division and clonal expansion of the immune cells in response to TB.

Adolescent↗
PubMed1999

The identification of myriocin-binding proteins.

BACKGROUND: Myriocin is a natural product that potently induces apoptosis of a murine cytotoxic T lymphocyte cell line (CTLL-2) and inhibits a serine palmitoyltransferase (SPT) activity that has been detected in cell extracts and is thought to initiate sphingolipid biosynthesis. Because SPT has never been biochemically purified and a comprehensive appraisal of myriocin-binding proteins has not been conducted, we isolated specific targets using myriocin-based affinity chromatography. RESULTS: Myriocin derivatives were synthesized and evaluated using CTLL-2 proliferation and SPT activity assays. Guided by these results, affinity chromatography matrices were prepared and two specific myriocin-binding proteins were isolated from CTLL-2 lysates. Analyses of these polypeptides establish conclusively that they are murine LCB1 and LCB2, mammalian homologs of two yeast proteins that have been genetically linked to sphingolipid biosynthesis. CONCLUSION: The ability of myriocin-containing matrices to bind factors that have SPT activity and the exclusive isolation of LCB1 and LCB2 as myriocin-binding proteins demonstrates that the two proteins are directly responsible for SPT activity and that myriocin acts directly upon these polypeptides.

Acyltransferases↗
PubMed1999

Once-a-month treatment with a combination of mifepristone and the prostaglandin analogue misoprostol.

In this two centre study, the efficacy of 200 mg mifepristone orally followed 48 h later by 0.4 mg misoprostol orally for menstrual regulation was investigated. The dose of mifepristone was taken the day before the expected day of menstruation. Each volunteer was planned to participate for up to 6 months. A plasma beta human chorionic gonadotrophin (HCG) was measured on the day of mifepristone intake. The study was disrupted prematurely due to low efficacy. In 125 treatment cycles the overall pregnancy rate was 17.6% (22 pregnancies) and the rate of continuing pregnancies (failure) was 4.0%. Eight women discontinued the study due to bleeding irregularities which were seen in 15 cycles (12%). These effects on bleeding pattern made the timing of treatment day difficult. Late luteal phase treatment with a combination of mifepristone and misoprostol is not adequately effective for menstrual regulation.

Abortifacient Agents, Nonsteroidal↗
PubMed1999

Pseudosparing of the endplate: a potential pitfall in using MR imaging to diagnose infectious spondylitis.

OBJECTIVE: The objective of this study was to describe a potential pitfall in using MR imaging to diagnose infectious spondylitis called "pseudosparing" of the endplate, in which the diseased endplate appears to be better defined than a healthy endplate. CONCLUSION: Poor definition of the endplate is a classic radiographic finding in infectious spondylitis; on MR imaging, however, increased conspicuity, or "pseudosparing," was common in our study. Pseudosparing occurs when the normal chemical shift artifact seen in healthy endplates is lost as a result of infiltration of the bone marrow by a pathologic process.

Adult↗
PubMed1999

Tyrosine kinase inhibition affects type 1 angiotensin II receptor internalization.

Growth factor receptors activate tyrosine kinases and undergo endocytosis. Recent data suggest that tyrosine kinase inhibition can affect growth factor receptor internalization. The type 1 angiotensin II receptor (AT1R) which is a G-protein-coupled receptor, also activates tyrosine kinases and undergoes endocytosis. Thus, we examined whether tyrosine kinase inhibition affected AT1R internalization. To verify protein tyrosine phosphorylation, both LLCPKCl4 cells expressing rabbit AT1R (LLCPKAT1R) and cultured rat mesangial cells (MSC) were treated with angiotensin II (Ang II) [1-100 nM] then solubilized and immunoprecipitated with antiphosphotyrosine antisera. Immunoblots of these samples demonstrated that Ang II stimulated protein tyrosine phosphorylation in both cell types. Losartan [1 microM], an AT1R antagonist, inhibited Ang II-stimulated protein tyrosine phosphorylation. LLCPKAT1R cells displayed specific 125I-Ang II binding at apical (AP) and basolateral (BL) membranes, and both AP and BL AT1R activated tyrosine phosphorylation. LLCPKAT1R cells, incubated with genistein (Gen) [200 microM] or tyrphostin B-48 (TB-48) [50 microM], were assayed for acid-resistant specific 125I-Ang II binding, a measure of Ang II internalization. Both Gen (n = 7) and TB-48 (n = 3) inhibited AP 125I-Ang II internalization (80+/-7% inhibition; p<0.025 vs. control). Neither compound affected BL internalization. TB-1, a non-tyrosine kinase-inhibiting tyrphostin, did not affect AP 125I-Ang II endocytosis (n = 3), suggesting that the TB-48 effect was specific for tyrosine kinase inhibition. Incubating MSC with Gen (n = 5) or herbimycin A [150 ng/ml] (n = 4) also inhibited MSC 125I-Ang II internalization (82+/-11% inhibition; p<0.005 vs. control). Thus, tyrosine kinase inhibition prevented Ang II internalization in MSC and selectively decreased AP Ang II internalization in LLCPKAT1R cells suggesting that AP AT1R in LLCPKAT1R cells and MSC AT1R have similar endocytic phenotypes, and tyrosine kinase activity may play a role in AT1R internalization.

Angiotensin II↗
PubMed1999

Inhibition of vascular endothelial cell morphogenesis in cultures by limbal epithelial cells.

PURPOSE: To study the in vitro angiogenic activity of human conjunctival and limbal epithelial cells and conjunctival, limbal, and corneal fibroblasts in a three-cell-type coculture model. METHODS: Human umbilical vein endothelial cells (EC) were cocultured with epithelial cells, fibroblasts, or epithelial cells and fibroblasts to test their effect on EC morphogenesis. Neutralizing antibodies to some known angiogenic factors were added to the culture to see whether the EC morphogenesis may be blocked by a particular antibody. RESULTS: Conjunctival and limbal epithelial cells exhibited very little or no stimulatory effect on EC tube formation when examined in an EC- epithelial cell coculture system. In contrast, conjunctival, limbal, and corneal fibroblasts all promoted EC morphogenesis when examined under the same culture conditions. Fibroblast-induced EC morphogenesis was inhibited by addition of anti-vascular endothelial growth factor (VEGF) and/or anti-basic fibroblast growth factor (bFGF) antibodies to the culture medium. In the three-cell-type coculture system consisting of ECs, fibroblasts, and epithelial cells, limbal epithelial cells (but not conjunctival epithelial cells) exhibited a strong inhibitory effect on fibroblast-induced EC tube formation. CONCLUSIONS: The proangiogenic activity of ocular surface fibroblasts is probably mediated through a paracrine mechanism by VEGF and bFGF. Limbal epithelial cells, but not conjunctival epithelial cells, inhibit fibroblast-stimulated angiogenesis.

Adolescent↗
PubMed1998

Epoxyeicosatrienoic acids and their sulfonimide derivatives stimulate tyrosine phosphorylation and induce mitogenesis in renal epithelial cells.

In our present studies utilizing a well characterized proximal tubule cell line, LLCPKcl4, we determined that all four EET regioisomers (5,6-EET, 8,9-EET, 11,12-EET, and 14,15-EET) stimulated [3H]thymidine incorporation, with 14,15-EET being the most potent. In contrast, no mitogenic effects were seen with arachidonic acid, other cP450 arachidonate metabolites (12R-hydroxyeicosatetraenoic acid (12R-HETE), 14,15-dihydroxyeicosatrienoic acid (14,15-DHET), or 20-HETE), or lipoxygenase metabolites (5S-HETE, leukotriene B4, or lipoxin A4). We found that their metabolically more stable sulfonimide (SI) analogs (11,12-EET-SI and 14,15-EET-SI) were also potent mitogens. In addition 14,15-EET-SI also increased cell proliferation as well as expression of both c-fos and egr-1 mRNA. The protein kinase C and A inhibitors, H-7 and H-8, or the cyclooxygenase inhibitor, indomethacin, had no effect upon 14, 15-EET-induced [3H]thymidine incorporation, but the selective tyrosine kinase inhibitor, genistein, significantly inhibited it. Immunoprecipitation and immunoblotting demonstrated increased tyrosine phosphorylation of PI3-kinase and epidermal growth factor receptor (EGFR) within 1 min of EET administration. EETs also stimulated association of PI3-kinase with EGFR. PI3-kinase inhibitors, wortmannin and LY 294002, markedly inhibited 14, 15-EET-SI-stimulated [3H]thymidine incorporation. In addition, 14, 15-EET-SI administration stimulated tyrosine phosphorylation of src homologous and collagen-like protein (SHC) and association of SHC with both growth factor receptor-binding protein (GRB2) and EGFR. Mitogen-activated protein kinase was also activated within 5 min. Pretreatment of the cells with the mitogen-activated protein kinase kinase inhibitor, PD98059, inhibited the 14,15-EET-SI-stimulated [3H]thymidine incorporation. Moreover, immunoblotting indicated that 14,15-EET stimulated tyrosine phosphorylation of the specific pp60(c-src) substrate p120 and c-Src association with EGFR. 14, 15-EET increased src kinase activity within 1 min. Our data indicate that EETs are potent mitogens for renal epithelial cells, and the mitogenic effects of the EETs are mediated, at least in part, by the activation of Src kinase and initiation of a tyrosine kinase phosphorylation cascade.

8,11,14-Eicosatrienoic Acid↗
PubMed1998

Differential effects of aneugens and clastogens on incidences of multinucleated cells and of micronucleate cells in Chinese hamster lung (V79) cell line in vitro.

Two aneugens, vinblastine (0.025-0.4 microgram/ml) and colchicine (0.05-0.4 microgram/ml), and two clastogens, mitomycin C (0.05-0.4 microgram/ml) and cyclophosphamide (1-16 micrograms/ml) were applied respectively to the micronucleus test in Chinese hamster lung (V79) cells in vitro, and the frequency of multinucleated cells (Fmu) and that of micronucleate cells (Fmi) in each group were observed. The results showed that at relatively high concentrations, all four agents increased both Fmu and Fmi, but the ratios of Fmu to Fmi in groups of the two aneugens (average of 2.2, 2.8, respectively) were much (10-30 folds) higher than that in groups of the two clastogens (0.09, 0.20). The difference between aneugens and clastogens in the above ratio was much more remarkable than that in areas of micronuclei (only 1.6-2.5 folds for the latter). At relatively low concentrations, the two clastogens increased only Fmi (but not Fmu), while the two aneugens increased only Fmu (but not Fmi). This indicates that the induction of multinuclei by aneugens may be more sensitive than by clastogens, and the induction of micronuclei by clastogens may be more sensitive than by aneugens. So, it is possible for the ratio of Fmu to Fmi to become a simple and sensitive (though indirect) index for distinguishing aneugens from clastogens. Further studies with other mutagens and (or) other cell types will be needed to confirm the deduction. As no difference in frequency of polyploid cells was observed between control group and each treatment, the multinucleation does not seem related to endoreduplication of chromosomes.

Aneuploidy↗