The effect of track structure on the induction of chromosomal aberrations in murine cells

Maternal pre-pregnancy obesity is a risk factor for pre-eclampsia (proteinuric hypertension in pregnancy) among North American and European women. We studied the relationship between maternal obesity and risk of pre-eclampsia among Zimbabwean women. A case-control study was conducted at Harare Maternity Hospital, Harare, Zimbabwe, between June 1995 and April 1996. Study participants were 144 women with pre-eclampsia and 194 normotensive women serving as controls. Maternal weight, height and mid-arm circumference were measured and recorded during study participants' postpartum hospital admission. Maternal mid-arm circumference, considered to be relatively stable during pregnancy among women of developing countries, was used as the primary indicator of maternal pre-pregnancy obesity. Logistic regression procedures were used to estimate odds ratios and 95% confidence intervals. There were linear trends in risk of pre-eclampsia with increasing mid-arm circumference, increasing weight and increasing body mass index. After adjusting for potential confounding factors, women in the highest quintile for mid-arm circumference (28-39 cm) were 4.4 times more likely to have had their pregnancy complicated by pre-eclampsia than women in the lowest quintile (21-23 cm). Odds ratios of similar magnitude were observed for the other anthropometric measures. To our knowledge, this is the first study to demonstrate a positive association between maternal obesity and pre-eclampsia risk in a black African population. Biological mechanisms thought to explain this relatively consistent epidemiological finding include endothelial cell injury, possibly resulting from hyperlipidaemia.     

Oxygen and light effects on chromosomal aberrations in mouse cells in vitro

An image analysis of the ITPA and WISC Subtest Scores of three diagnostic groups was done. In two of the diagnostic groups, a regular classroom group and an LLD group, a general linguistic factor, a visual-motor factor, and a mediation factor appeared to emerge. A general ITPA factor, a general WISC factor, and an expressive factor were extracted from the mentally retarted group's data. Differences among the factors of diagnostic groups were observed and commented upon after a canonical correlation of factor loading matrices.     

A new choleretic effect of folinic acid

BACKGROUND/AIMS: In the chemotherapy of recurrent gastric cancer with 5-fluorouracil and folinic acid, an interesting phenomenon, the reduction of jaundice and improvement of liver function, was observed. The aim of this study was to investigate the mechanism of this phenomenon, and to confirm a choleretic effect of folinic acid. METHODOLOGY: The bile duct of anesthetized rats was catheterized, and bile was collected. Bile volume and total bile acid production following intraperitoneal administration of folinic acid were determined and compared to those of control rats. RESULTS: Both bile volume and total bile acid production increased following intraabdominal administration of folinic acid. CONCLUSIONS: Folinic acid has a newly described pharmacologic effect of stimulating bile acid-dependent choleresis. It is possible that folinic acid may become a new drug for the treatment of jaundice or for the improvement of overall liver function.     

Inhibitory effect of crocetin on intracellular nucleic acid and protein synthesis in malignant cells

The possibility that dietary intake of diverse naturally occurring compounds may influence the occurrence of cancer is receiving considerable scientific attention. Previously, it was reported that an extract (Crocus sativus), which contains carotenoids, had an antitumor effect and inhibited colony formation and nucleic acid synthesis by malignant human cells. Epidemiological and experimental research has indicated that carotenoids might act as antitumor agents. We have studied crocetin, a carotenoid isolated from saffron, which has been shown to have biological activity. In our experiments we utilized three malignant human cell lines: HeLa (cervical epitheloid carcinoma), A549 (lung adenocarcinoma) and VA13 (SV-40 transformed fetal lung fibroblast) cells. The effect of crocetin on colony formation and cellular DNA, RNA and protein synthesis in these cells has been examined. Incubation of these cells with crocetin for 3 h caused a dose-dependent inhibition of nucleic acid and protein synthesis. Crocetin also had a dose-dependent inhibitory effect on DNA and RNA synthesis in isolated nuclei and suppressed the activity of purified RNA polymerase II.     

Analysis of chromosomal aberrations, sister chromatid exchanges and micronuclei among power linesmen with long-term exposure to 50-Hz electromagnetic fields

Chromosomal aberrations, sister chromatid exchanges (SCEs), replication indices and micronuclei in peripheral blood lymphocytes were analysed among 27 nonsmoking power linesmen with considerable long-term exposure to 50-Hz electromagnetic (EM) fields, and among 27 nonsmoking telephone linesmen serving as a reference group, pairwise matched with the exposed workers for age and geographical region. Blood samples from the two groups were collected, cultured and analysed in parallel. No differences between the groups were observed on analysis of SCEs, replication indices or micronuclei. However, the mean rate of lymphocytes with chromatid-type breaks was higher among the power linesmen (0.96% gaps excluded, 1.41% gaps included) than among the reference group (0.44% and 0.70%, respectively). The excess of aberrant cells was concentrated among those power linesmen who had worked earlier in their life. Although the interpretation is somewhat complicated by the confounding effect of previous smoking, these results suggest that exposure to 50-Hz EM fields is associated with a slight increase in chromatid breaks.     

Involvement of telomeric sequences in chromosomal aberrations

The genomes of higher eukaryotes are not homogeneous in terms of structure or function. Many examples of chromosomal regions particularly prone to involvement in aberrations have been reported. The molecular structures of some of these regions have now been determined, most notably the folate-sensitive fragile sites and FRA16B-a distamycin A-sensitive fragile site. In addition, a number of cytological studies suggest that telomeric sequences can in some circumstances be involved in chromosomal aberrations more frequently than expected. Here, the roles of telomeric DNA sequences, both terminal and interstitial, and telomerase in chromosomal aberration formation are reviewed.     

Oxidative stress-induced cadmium resistance in Chinese hamster V79 cells

Injections of an aqueous extract of winter cherry fruits (Physalis alkekengi) to adult female cycling rats by an intraperitoneal route resulted in the diminution of the pituitary lysyl-aminopeptidase (Lys-AP) activity by 50% and that of the basomedial hypothalamus (BMH) by 45%. Administration of daily doses of 3.75, 7.5, and 15 micrograms beta-estradiol for a period of 5-8 days to such animals increased pituitary Lys-AP activity from 31% to 61.5% and that of BMH from 20% to 87%, respectively. Administration of the same doses of beta-estradiol along with a given dose of the aqueous extract for 7-8 days diminished Lys-AP inhibitory effect of the extract in both the pituitary and BMH and eventually, at the highest dose of beta-estradiol, increased the pituitary enzyme activity by 9% and that of BMH by 5%. It is concluded that Lys-AP enzymes of both tissues, being estrogen-induced proteins, are inhibited by the estrogen antagonistic principle of the winter cherry aqueous extract. It is further suggested that BMH Lys-AP activity may be used as an enzyme marker for the action of beta-estradiol in hypothalamus.     

Genotoxicity of trophosphamide in mouse germ cells: assessment of micronuclei in spermatids and chromosome aberrations in one-cell zygotes

We have used the muscle history dependence of the sensitivity of muscle spindles to stretch, to provide evidence for their contribution to kinaesthesia, the sense of position and movement. Stretch sensitivity is altered depending on whether or not slack has been introduced in intrafusal fibres [13]. At the human elbow joint detection threshold was measured to passive movements applied at different speeds to the forearm after a conditioning co-contraction of muscles of the upper arm, with the arm held either flexed ('hold short') or extended ('hold long'). Test measurements were made with the elbow joint at 90 degrees. For the three speeds of movement, 2 degrees s-1, 0.2 degree s-1 and 0.02 degree s-1, after 'hold short' conditioning thresholds were lower for movements into extension, after 'hold long' conditioning they were lower for movements into flexion. It is concluded that when muscle conditioning introduces slack in the intrafusal fibres of muscle spindles, this must be taken up by the test movements before they can be detected by the subject. It means that whenever detection thresholds to passive movements are measured at a joint, the contraction history of the muscles acting at that joint must be taken into account.     

In vivo chromosomal aberrations in bone marrow cells of rats treated with Marshal

In this study, the cytogenetic effects of Marshal (insecticide/nematocide) were investigated in bone marrow cells of rats. The results obtained from animals treated with Marshal were compared with the results of animals treated with ethyl carbamate (EC) and with controls. Concentrations of 12.5, 25 and 50 mg/kg b.wt. of Marshal and 100, 200 and 400 mg/kg b.wt. of EC were used and animals were sampled at three different times (6, 12 and 24 h). Marshal increased the number of chromosomal aberrations (CA) per cell, and the number of cells with abnormalities, at all concentrations and treatment times. Generally, Marshal could increase the number of the abnormal cells and the formation of CA as easily as EC. However, Marshal, at 50 mg/kg b.wt. did not increase the frequency of abnormal cells or CA as strongly as EC, at 400 mg/kg b.wt. for 6 h. Marshal also decreased the mitotic index (MI) compared with the control group. The MI was higher in the group treated with Marshal for 6 h than that treated with EC. However, the effects of Marshal and EC on the MI in the groups treated for 12 and 24 h were similar. We found that the effect of Marshal on the formation of abnormal cells and CA was dependent on concentration and treatment time.     

Mutagenicity of oxidative DNA damage in Chinese hamster V79 cells

We have investigated the mutagenicity of oxidative DNA damage induced in V79 Chinese hamster lung fibroblast, and measured 8-hydroxydeoxyguanosine (8OHdG) levels as an indicator of this damage. A hydroxyl radical generator, N,N'-bis(2-hydroxyperoxy-2-methoxyethyl)-1,4,5,8-naphthalene-tetra -carboxylic-diimide (NP-III), induced 8OHdG in V79 upon irradiation with 366 nm ultraviolet light (UV) for 15 min. 8OHdG was determined by HPLC with electrochemical detection after anaerobic sample processing. The 8OHdG level in the cells treated without NP-III was 0.49 per 10(5) dG, whereas levels in the cells treated with 5, 10 or 20 microM NP-III and UV irradiation were 1.84, 4.06 or 6.95 per 10(5) dG, respectively. The 8OHdG induced by 20 microM NP-III with UV irradiation decreased rapidly, and the half-life of the induced 8OHdG was approximately 6 h. NP-III with UV irradiation also induced DNA strand breaks in all cells uniformly, as determined by single cell gel assay. Mutant frequencies at the hypoxanthine-guanine phosphoribosyltransferase (hprt) locus in V79 were determined as the number of 6-thioguanine-resistant cells per 10(6) cells. Mutant frequency of the cells without NP-III was 8.0, and frequencies of the cells treated with 5, 10 or 20 microM NP-III and UV irradiation were 14.9, 20.6 or 24.7 respectively. Treatment with 20 microM NP-III and UV irradiation decreased the cell number, determined 3 days after the treatment, to 20.8%. These findings indicate that acutely induced oxidative DNA damage including mutagenic 8OHdG is only weakly mutagenic in V79.     

Comparison of chromosomal damage induced by X-rays and Ar ions with an LET of 1840 keV/micrometer in G1 V79 cells

Wound healing in the adult is commonly compromised by excessive scar formation. In contrast, fetal wound healing is a regenerative process characterised by the conspicuous absence of scarring. Available evidence suggests that phenotypic differences between fetal and adult fibroblasts are important determinants of these distinct modes of tissue repair. In this context, a number of groups (including our own) have documented differences between fetal and adult fibroblasts with respect to such potentially relevant characteristics as migratory activity, motogenic response to cytokines and the synthesis of motility factors, cytokines and matrix macromolecules. The oral mucosa appears to be a privileged site in the adult in that it continues to display a fetal-like mode of wound healing. Data are presented in this review indicating that a subpopulation of gingival fibroblasts expresses several 'fetal-like' phenotypic characteristics. These observations are discussed in terms of both the continued expression of a fetal-like mode of wound healing in the oral mucosa and the possible differential involvement of distinct fibroblast subpopulations in the progression of periodontal disease.     

Nuclear architecture and the induction of chromosomal aberrations

Progress in fluorescence in situ hybridization, three dimensional microscopy and image analysis has provided the means to study the three-dimensional structure and distribution of chromosome territories within the cell nucleus. In this contribution, we summarize the present state of knowledge of the territorial organization of interphase chromosomes and their topological relationships with other macromolecular domains in the human cell nucleus, and present data from computer simulations of chromosome territory distributions. On this basis, we discuss models of chromosome territory and nuclear architecture and topological consequences for the formation of chromosome exchanges.     

Molecular mechanisms for the induction of chromosomal aberrations in CHO cells heated in S phase

During the past 20 years, 972 microvascular transplantations have been performed for 783 patients, with an overall failure rate of 6.2 percent. Fifty-four of the 60 failed transplantations were available for long-term follow-up and were retrospectively reviewed with respect to the original indications for transplantation, the number, and the type of salvage procedures performed following transplant failure. This study illustrates that the choice of salvage procedures performed following transplant failure depends on the original indications, the location, and the severity of the resultant wound. Failure following transplantation for coverage of contour defects or unstable wounds can often be managed by non-microsurgical methods. In contrast, when the indications for transplantation included the transfer of specialized tissues for thumb or digit reconstruction, the restoration of motor or sensory function, or the coverage of a limb-threatening wound, requirements for reconstruction could be satisfied only by a second successful tissue transplant. Eighteen of the 54 cases underwent an additional transplantation, with an 89 percent success rate.     

Numerical chromosomal aberrations in transition-zone carcinomas of the prostate

PURPOSE: Prostatic carcinomas arising in the transition zone (TZ) are thought to differ from the more frequent cancers of the peripheral zone (PZ) with regard to morphology and biologic behavior. It is unclear, however, whether the differences are reflected in genetic alterations. MATERIALS AND METHODS: We assessed numerical aberrations of chromosomes 7, 8, 10, 17, and X with interphase cytogenetics in 10 radical-prostatectomy specimens containing exclusively TZ cancers larger than 0.5 cm.3 and in 10 additional specimens containing both TZ and PZ cancers larger than 0.5 cm.3 each. RESULTS: Of the 20 TZ carcinomas, 9 were completely disomic, 5 were at least focally tetrasomic but not aneusomic, and 6 were focally aneusomic. Ploidy correlated well with tumor volume (p = 0.0083), grade (p = 0.0064) and surgical margins (p = 0.0141) but not with preoperative prostate-specific antigen. A strong correlation was observed between the presence of low grade tumor (Gleason grade 4 or 5) and a nondiploid chromosomal status (p = 0.0001). In 10 cases there were also foci of PZ cancer larger than 0.5 cm.3, of which 4 were disomic, 3 were tetrasomic at the most, and 3 were aneusomic. The mean tumor volumes of disomic and aneusomic cancers differed significantly between TZ and PZ carcinomas (p = 0.0336 and 0.0476, respectively). CONCLUSIONS: Numerical chromosomal instability parallels tumor progression in TZ carcinomas of the prostate. However, our results indicate that PZ and TZ cancers differ in that the latter can reach larger volumes before histological dedifferentiation and aneusomy occur.     

Bio-antimutagenic activity of green tea catechins in cultured Chinese hamster V79 cells

The antimutagenic effects of green tea catechins, (-)-epicatechin gallate (ECg) and (-)-epigallocatechin gallate (EGCg) on induction of 6-thioguanine (6TG)-resistant mutations induced by 4-nitroquinolin 1-oxide (4NQO) were found in cultured Chinese hamster V79 cells. The antimutagenic activity of catechins was found only when cells were post-treated with catechins during the mutation expression time after treatment with 4NQO, and not found by simultaneous treatments with 4NQO and catechins. This bioantimutagenic activity of catechins were not observed in ethyl methanesulfonate (EMS)-induced mutations. This suggests that the antimutagenic effects of catechins may act intracellularly as bio-antimutagenic blocking agent or suppressive agent. These catechins had no effects on the cytotoxic activity of 4NQO in V79 cells, whether catechins were used in simultaneous treatment with or in post-treatment after 4NQO. This indicates that the antimutagenicity and anticytotoxicity to 4NQO may be caused by different mechanism(s).     

Effects of some diethylstilbestrol metabolites and analogs on cytotoxicity and aneuploidy induction in Chinese hamster V79 cells

We have previously reported the inhibitory effects of diethylstilbestrol (1) and optically active indenestrol derivatives on microtubule polymerization in vitro and their disruptive effect on cytoplasmic microtubules and cytotoxicity in cultured Chinese hamster V79 cells. In the present study, the cytotoxicities of (+-)-diethylstilbestrol oxide (2), (+)-, (-)- and (+-)-monomethyl ethers (4) of 2, (+-)-dimethyl ether (5) of 2, diethylstilbestrol pinacolone (3), E,E-dienestrol (6), Z,Z-dienestrol (7), meso-hexestrol (8), a mixture of (1R,1'S)4-hydroxyhexestrol and (1R,1'S)4'-hydroxyhexestrol (9), and the 4-hydroxy derivative (10) of diethylstilbestrol dimethyl ether were investigated in Chinese hamster V79 cells. The results indicated that the cytotoxic activity of 10 was the strongest of the compounds tested, although its activity was the almost same as that of 1. Moreover, as the activity of (-)-4 was greater than those of 2 and 1 monomethyl ethers, the effect of 4 on cytotoxic activities was elucidated. In conclusion, the present results indicate that the cytotoxic activities of hydroxylated metabolites are greater than those of each mother compound, although epoxidation of 1 leads to a product which can be broken down more readily than the parent compound.     

Mutagenicity of kaempferol in V79 cells: the role of cytochromes P450

The flavonol kaempferol is widely found in the diet and is directly mutagenic in some short-term tests, such as the induction of chromosomal aberrations in eukaryotic cells. The presence of exogenous metabolizing systems enhances its mutagenicity. We have evaluated the role of cytochromes P450 in the induction of chromosomal aberrations by kaempferol in V79 cells. The results obtained suggest that there is a time-dependent biotransformation of kaempferol to quercetin, by cytochromes P450, as assessed by high pressure liquid chromatography. Quercetin seems to contribute to the mutagenicity of kaempferol in the presence of microsomal metabolizing systems. On the other hand, the direct induction of chromosomal aberrations by kaempferol does not seem to depend on the production of reactive oxygen species.     

Analysis of electroporation-induced genetic damages in V79/AP4 Chinese hamster cells

Electroporation is a recent technique used to introduce exogenous DNA into eukaryotic cells. It is important to establish that the gene of interest is transferred into a functional, non-mutated recipient cell. V79/AP4 Chinese hamster cells were exposed to high-voltage pulsed electric fields and some biological and genetic effects were measured. The results showed that cytotoxicity was related in a dose-dependent manner to the number of applied pulses. Thioguanine-resistant colony-forming cells as well as chromosomal aberrations were also induced whereas ouabain resistants and sister-chromatid exchanges were not or slightly induced. Spontaneous and electroporation-induced clones that were phenotypically TGR/HATS were used to investigate the hprt locus. Molecular screening of the locus showed that the number of deleted exons was significantly higher in induced than in spontaneous TG-resistant clones, suggesting that the genetic damages induced by electroporation concern the loss of regions well over the size of the hprt locus.