Quasi-isentropic compression of LiH above 400 GPa using magnetocumulative generator.

The knowledge of high-pressure behavior of LiH is significant for the validation of fundamental theoretical models and applications in thermonuclear materials and potential energy supplies. The compressibility of 7LiH under isentropic compression at high pressure was investigated experimentally and theoretically. The experimental technique for quasi-isentropic compression with low-density materials was developed using the magnetocumulative generator CJ-100 and x-ray flash radiography. The x-ray images and extracted interface of the sample target in dynamic flash radiography experiments were obtained. According to each interface size of the target both before and after compression, the compression ratio of 7LiH and reference material aluminum was obtained. The density of the reference and using its known isentropic curve provide the pressure in the reference. The pressure in 7LiH was deduced from the pressure in the reference and using the calculated gradient correction factor. The quasi-isentropic data point at 438 GPa was obtained experimentally. A semiempirical three-term complete equation of state was constructed and validated for 7LiH using the theory of Mie-Grüneisen-Debye with experimental data from the literature. The quasi-isentrope data point is reasonably consistent with the theoretical results. The quasi-isentropic experimental techniques and results broaden the existing research scope and are practical and helpful to further validate theoretical models in the future.

Apolipoprotein B-48 is the product of a messenger RNA with an organ-specific in-frame stop codon.

The primary structure of human apolipoprotein (apo) B-48 has been deduced and shown by a combination of DNA excess hybridization, sequencing of tryptic peptides, cloned complementary DNAs, and intestinal messenger RNAs (mRNAs) to be the product of an intestinal mRNA with an in-frame UAA stop codon resulting from a C to U change in the codon CAA encoding Gln2153 in apoB-100 mRNA. The carboxyl-terminal Ile2152 of apoB-48 purified from chylous ascites fluid has apparently been cleaved from the initial translation product, leaving Met2151 as the new carboxyl-terminus. These data indicate that approximately 85% of the intestinal mRNAs terminate within approximately 0.1 to 1.0 kilobase downstream from the stop codon. The other approximately 15% have lengths similar to hepatic apoB-100 mRNA even though they have the same in-frame stop codon. The organ-specific introduction of a stop codon to a mRNA appears unprecedented and might have implications for cryptic polyadenylation signal recognition and RNA processing.

[Causes and management of frontal sinusitis after transfrontal craniotomy].

Objective:The aim of this study is to investigate the causes and the strategy of frontal sinusitis after transfrontal craniotomy by endoscopic frontal sinus surgery and traditional surgery with facial incision. Method:A total of thirty-four patients with frontal sinusitis after transfrontal craniotomy were admitted, with the symptom of purulence stuff, headache and upper eyelid discharging. The onset time was 2.6 years on average. The frontal sinus CT and MRI images showed frontal sinusitis. Twenty-seven patients were treated with endoscopic frontal sinus surgery, and seven patient was treated with combined endoscopic and traditional frontal sinus surgery. In the revision surgery, the bone wax and inflammatory granulation tissue were cleaned out in both operational methods. The cure standard was that the postoperative frontal sinus inflammation disappeared and the drainage of the volume recess was unobstructed. Result:Thirty-four patients had a history of transfrontal craniotomy, and there was a record of bone wax packing in every operation. Among twenty-seven patients with endoscopic frontal sinus surgery, Twenty-five cases cured and two cases were operated twice. Seven patients were cured with combined endoscopic and traditional frontal sinus surgery. Conclusion:The frontal sinusitis after transfrontal craniotomy may be related to the inadequate sinus management, especially bone wax to be addressed to the frontal sinus ramming leading to frontal sinus mucosa secretion obstruction and poor drainage. Endoscopic frontal sinus surgery is a way of minimally invasive surgery. The satisfying curative effect can be obtained by endoscopic removal of bone wax, inflammatory granulation tissue, and the enlargement of frontal sinus aperture after exposure to the frontal sinus, and some cases was treated with both operation method.

Preparation of bioactive nanotitania ceramics with biomechanical compatibility.

In this article, bioactive nanotitania ceramics with biomechanical compatibility was prepared by using an additive of hydroxyapatite or MgO as particle growth inhibitor. After sintering at 1000 degrees C, the particle size of nanotitania ceramics prepared by using HA as additive (HT) was much smaller than that prepared by using MgO as additive (MT). In simulated body fluid (SBF), HT could induce apatite formation in 4 days, while no apatite could be found on MT even after it was soaked in SBF for 14 days. After Ros17/28 osteoblasts were cultured on the materials for 1, 4, and 6 days, MTT results showed that the osteoblasts on the HT differentiated faster than that on the MT. Mechanical tests results showed that the bending and compressive strength of HT were 160 and 200 MPa, while those of MT were 70 and 88 MPa, respectively. These results demonstrated that it is suitable to prepare bioactive nanotitania ceramics, with biomechanical compatibility, by using HA as particle growth inhibitor.

The primary structure of human apolipoprotein A-IV.

Human apolipoprotein (apo) A-IV was purified from chylous ascites fluid. Proteolytic peptides produced by trypsin and Staphylococcus aureus V8 proteinase digestions were purified by high-performance liquid chromatography and sequenced. Human apoA-IV contains 376 amino acid residues. The peptide-derived sequence generally matches two previously reported DNA-derived amino acid sequences except for discrepancies in five positions. In order to examine these discrepancies further, one complete apoA-IV cDNA clone and another partial clone were sequenced. Comparison of all the available information indicates that the peptide-derived sequence reported here is accurate. Sequencing errors probably account for some of the discrepancies between the two primary sequences predicted by earlier nucleotide analyses. In certain positions, however, bona fide sequence heterogeneity or cloning artifact cannot be excluded.

Nonselective cation current in rabbit ventricular myocytes.

Currents contributing repolarization in rabbit ventricular myocytes are very complex because the I(to.s) covers almost the whole repolarization phase of the action potential. The other components of repolarizing currents, such as I(Kr) and I(Ks), are small. In the present work, with whole-cell patch-clamp technique, a clear evidence was provided for the existence of a hitherto unreported, voltage-dependent, nonselective cation current (NSCC) in rabbit ventricular myocytes. Na(+), K(+), and Cs(+) can permeate through the nonselective cation channel and the NSCC can be blocked by Gd(3+). The channels are sensitive to Ca(2+), Mg(2+)-free, and insulin in bathing solution. Activation of NSCC may provide complex effects on action potential configuration depending on the basal conditions and the experimental situations. Considering the voltage dependence and rapid activation kinetics of this current, we speculate that this current can provide an important influence on all repolarization phases of the action potential as well as contribute to the resting membrane potential in rabbit ventricular myocytes. In addition, it is conceivable that, under certain pathophysiological conditions (e.g., ischemia or excessive mechanical stress), the sensitivity of the channels could be altered in such a way that the conductance opens even in the presence of physiological Ca(2+), Mg(2+), and insulin. It might be an important factor on the repolarization of the action potential. Changes in NSCC may lead to an induction or inhibition of arrhythmia.

Intracellular pH-induced fluorescence used to track nanoparticles in cells.

A nanoparticle with pH-induced fluorescence was reported for intracellular tracking. The fluorescence was evoked by the isomerization of the ring-closed form spiropyran (SP) to the ring-open form merocyanine (MC) in the weak acidic environment of cells. The SP-MC switch accelerated the dissociation of nanoparticles to trigger the release of trapped paclitaxel.

The complete amino acid sequence of proapolipoprotein A-I of chicken high density lipoproteins.

The complete amino acid sequence of proapolipoprotein (proapo) A-I of chicken high density lipoproteins was determined by sequencing overlapping peptides produced by trypsin, S. aureus V8 protease, and cyanogen bromide cleavage. There are 240 amino acid residues in mature chicken apoA-I. By direct sequence analysis of a cyanogen bromide peptide, we also determined the sequence of a 6-amino-acid prosegment which is present at approx. 10% the molar amount of the mature peptide in chicken plasma. Sequence comparison among apoA-I from chicken, human, rabbit, dog and rat, and secondary structure analysis indicate that while the degree of sequence homology is only moderate (less than 50% between chicken and man), there is good conservation of apoA-I secondary structure, especially in the N-terminal two-thirds of the protein in these widely separated species.

Oxidative modifications of apoB-100 by exposure of low density lipoproteins to HOCL in vitro.

Although the products of oxidation of the lipid components of LDL have been studied extensively, much less is known about the specific products of oxidative modification of the apoprotein. We reacted native LDL and LDL that had been treated with HOCl with 2,4-dinitrophenylhydrazine (DNPH), delipidated and trypsinized the protein, and analyzed the products by HPLC. Although tryptic digests of native LDL and LDL oxidized by limited quantities of HOCl showed similar patterns by HPLC with detection at 220 nm, oxidized LDL showed several discrete peaks at 365 nm, which is characteristic of hydrazones formed with aldehydes and ketones, commonly termed protein carbonyls. Native LDl showed no peaks in the chromatograms at 365 nm. Peptides absorbing at 365 nm were isolated by HPLC and characterized. In most cases, the probable sites of modification on the peptides could be implied by failure of an anticipated amino acid to appear in the expected sequence. Of the 14 peptides isolated and characterized to date, eight peptides contained Cys residues. In other peptides, Lys, Trp, and Met were identified as amino acid residues apparently modified by HOCl treatment of LDL. Thirteen of the peptides identified are from trypsin-releasable peptides located on the surface of unoxidized native LDL. Our studies suggest a selective process of modification of apoB-100 by HOCl and the approaches used in the present studies should be useful for the characterization of the mechanisms of oxidation of this and other proteins.

Oxidation of bovine beta-casein by hypochlorite.

We recently observed two 2,4-dinitrophenylhydrazine (DNPH)-reactive proteins of 40 and 120 kDa in the bronchoalveolar lavage fluids of rats exposed to >95% O(2) for 48 h. The N-terminal sequences of these proteins were both identical over 16 amino acids with rat beta-casein, which, in addition to its more common association with milk, is produced by cytotoxic T-lymphocytes, and has been found to have proinflammatory properties. Because of the inflammatory response that accompanies hyperoxic lung injury, we investigated the oxidation of bovine beta-casein by HOCl. Following exposure to HOCl at 4 degrees C for 15 min, derivatization with DNPH, washing, and digestion with trypsin, the resultant peptides were separated by reverse-phase HPLC. One peptide isolated from a peak absorbing at 365 nm was identified as AVP(Y*)PQR, corresponding to amino acids 177-183 of bovine beta-casein. Analysis of the peptide by both electrospray and matrix assisted laser desorption ionization (MALDI) mass spectrometry identified a molecular ion MH+ of 1008.5 Da, which represents an increase of 178 Da from the calculated monoisotopic MH+ of the unmodified peptide of 830.45 Da. Daughter ion spectra of the doubly charged parent ion of the peptide further support the oxidation of the tyrosine to the quinone methide, with subsequent conversion to the corresponding hydrazone with DNPH. A second pair of products were identified as arising from oxidation of Y(193) within the tryptic peptide constituted by amino acids 184-202, and the corresponding chymotryptic cleavage side product, 191-202. Exposure of beta-casein to increasing amounts of HOCl revealed that M and Y residues were the most susceptible, although bovine beta-casein contains no C, and a single W, which would not be detected by our methods. The approach described in the present report can be used to evaluate the contributions of distinct mechanisms of oxidation in other experimental or pathological models.

Effects of gemfibrozil on very-low-density lipoprotein composition and low-density lipoprotein size in patients with hypertriglyceridemia or combined hyperlipidemia.

To examine the effects of gemfibrozil on very-low-density lipoprotein (VLDL) composition and low-density lipoprotein (LDL) size, five men with hypertriglyceridemia (HTG) alone and five men with HTG and hypercholesterolemia (combined hyperlipidemia, CHLP) were randomized for 8 weeks to Lopid SR (slow-release gemfibrozil; two 600-mg tablets once per day) or placebo in a crossover study. Drug therapy versus placebo significantly decreased plasma triglyceride (68%), and VLDL (77%), and significantly increased high-density lipoprotein cholesterol (25%); total cholesterol, apolipoprotein B and lipoprotein[a] concentrations did not change significantly. With drug, mean total apoE in plasma was 53% lower in patients with HTG and 39% lower in patients with CHLP. Gemfibrozil significantly affected VLDL composition: protein increased 26%, molar ratio of apoE to apoB reduced 48%, apoC-II increased 19%, and apoC-III decreased 9%. LDL cholesteryl ester significantly increased with drug treatment. VLDL subfractions were separated and classified as heparin binding (VLDLR, apoE rich) or nonbinding (VLDLNR-1 and VLDLNR-2, both apoE poor). All VLDL subfractions were significantly lower with drug therapy, and the differences for total VLDL and for VLDL subfractions were greater in patients with HTG. With placebo, VLDLR accounted for 41.8% of VLDL in HTG and 49.0% of VLDL in CHLP, reduced to 27.6% and 38.6%, respectively, with gemfibrozil. Taken together, these results suggest that treatment with gemfibrozil reduces plasma concentrations of VLDL and alters the apoprotein composition of VLDL in a manner that may favor LDL- and VLDL-receptor-mediated clearance of the apoE-rich VLDL subfraction, thereby reducing TG-rich particle concentrations, and possibly reducing risk for coronary heart disease.

Effect of serum concentration on the cytotoxicity and sister chromatid exchange induction by a chemical carcinogen and by a diesel particulate extract in V79 hamster cells.

The role of serum concentration on the cytotoxicity and on the sister chromatid exchange (SCE)-induction by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and by a diesel particulate extract (DPE), a complex mixture, has been carried out on V79 cells. An increase of the serum concentration in the medium decreases the toxicity of these chemicals, and especially when they are dispersed first in serum. Although no influence of serum concentration on the number of spontaneous SCEs occurring in control cells has been observed, the increase of serum concentration leads to a decrease in SCE's induction in treated cells. Our results show that serum can protect cells from the cytotoxic and mutagenic action of MNNG and diesel extract.

Cooperativity between free and N-(2-hydroxypropyl) methacrylamide copolymer bound adriamycin and meso-chlorin e6 monoethylene diamine induced photodynamic therapy in human epithelial ovarian carcinoma in vitro.

The purpose of this study was to determine the interaction between free (unbound) and N-(2-hydroxypropyl) methacrylamide (HPMA) copolymer bound adriamycin and meso-chlorin e6 monoethylene diamine (Mce6) induced photodynamic therapy in combination in their cytotoxic activities against human ovarian epithelial carcinoma (OVCAR-3) in vitro. The effects of each agent (free drugs and HPMA copolymer bound) alone and in combination were measured simultaneously utilizing two measures of cell viability: a) mitochondrial respiration via the 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide reduction (MTT) assay; and b) thymidine incorporation via the tritiated thymidine incorporation (TI) assay. These were performed at 72 and 144 h after drug exposure. Forty-eight hours from time zero (24 h after drug addition), the cells treated with Mce6 (free and HPMA copolymer bound) and controls were exposed to 650 nm light (13 min at 15 mW/cm2, 11.7 J/cm2). The calculated ED50 values by the MTT 72 h assay for adriamycin (A) and Mce6/light (C) were 1.5 microg/ml and 209 ng/ml, respectively. Adriamycin demonstrated progressive cellular toxicity over time in both assays. Mce6/light demonstrated initial damage at 72 h by MTT and TI which recovered by 144 h. Adriamycin and Mce6/light acted cooperatively to increase the percentage of cells inhibited. In combination, 21.3+/-1.5% MTT reduction activity was observed by free adriamycin and Mce6/light compared to the expected 27+/-5% (p<0. 0001) based on additivity. Twice the ED50 of adriamycin (2A=3 microg/ml) or Mce6/light (2C=418 ng/ml) resulted in only 42+/-3.6% and 39.2+/-2.0% activity, respectively (both p<0.0001 vs. combination). When Mce6/light at 10x ED50 (10C) was combined with 1x ED50 of adriamycin (1A), or the reciprocal combination, additional cooperativity was demonstrated. Compared to free drugs, both HPMA copolymer bound adriamycin (P-A) and HPMA copolymer bound Mce6/light (P-C) required a 10-fold increase in drug concentration to show equivalency with free drugs (A or C). Dose response curves demonstrated a reduced slope compared to free drugs in the same dose ranges. When P-A was added (1-10x free adriamycin ED50) to an effective concentration of P-C (10P-C: equivalent to 10x free Mce6 ED50) an improved long-term inhibition of OVCAR-3 cell multiplication was noted in both the MTT and TI 144 h assays. P-C (1-10x free Mce6 ED50) added to an effective concentration of P-A (10P-A: equivalent to 10x free adriamycin ED50) did not appear to significantly improve the efficacy profile of P-A. A and C in vitro appear to act independently and are cooperative in their combined toxicity against the human ovarian epithelial carcinoma cell line OVCAR-3. HPMA copolymer-adriamycin and Mce6 conjugates (P-A and P-C, respectively) inhibited growth of OVCAR-3 in vitro. HPMA copolymer-adriamycin added to HPMA copolymer-Mce6 improved the efficacy of HPMA copolymer-Mce6.

Isobolographic assessment of the interaction between adriamycin and photodynamic therapy with meso-chlorin e6 monoethylene diamine in human epithelial ovarian carcinoma (OVCAR-3) in vitro.

OBJECTIVE: Considering the differing mechanisms of cytotoxicity produced by adriamycin and the photosensitizer meso-chlorin e6 monoethylene diamine (Mce6) with light, the interaction of these agents in combination on human ovarian epithelial carcinoma (OVCAR-3 in vitro) was evaluated by dose and effect addition isobole analysis. METHODS: Mitochondrial respiration via the 3-(4,5-dimethyl thiazol-2 yl)-2,5-diphenyl tetrazolium bromide cleavage assay (MTT) and reproductive capacity via the tritiated thymidine incorporation assay (TI) were assessed 72 and 144 hours after exposure to adriamycin, Mce6, and light (650 nm), and to their combinations, in OVCAR-3 cells grown in vitro (20,000 cells per well). RESULTS: In the majority of assays, reproductive capacity was more sensitive to the drug(s) than was mitochondrial respiration (2-10x). Dose-addition isobole analysis showed synergy for the combination of 50% median effective dose (ED50) adriamycin with 50% ED50 Mce6/light in all assays (all P < or = .027). Antagonism was noted with the combination 25% ED50 adriamycin with 75% ED50 Mce6/light. Additivity and synergy were the predominant interactions for 75% ED50 adriamycin with 25% ED50 Mce6/light by dose-addition isobole analyses. Effect-addition isoboles showed a predominance of synergy, particularly for the combination 50% ED50 adriamycin with 50% ED50 Mce6/light. CONCLUSION: Synergy and additivity are the primary in vitro interactions for the combination of adriamycin and Mce6/light in the dosage range tested. Reproductive capacity is more sensitive to these agents than is mitochondrial respiration.

Primary structure of apoB-100.

Apolipoprotein B-100 (apoB-100) is the major protein in low-density lipoprotein (LDL) and contains the ligand for binding LDL to its cell surface receptor. Lipoprotein [a] (Lp[a]) is a lipoprotein that consists of LDL and apolipoprotein [a] (apo[a]). The primary structure of apoB-100 has been determined by a combination of recombinant DNA and protein sequencing methods. Using high-performance liquid chromatographic techniques, we have identified sulfhydryl and disulfide groups of apoB-100 from LDL. Sixteen of the 25 cysteine residues in apoB-100 exist in disulfide form. All 14 cysteine residues within the N terminal end of apoB-100 are linked in disulfide bridges. Using the fluorescent sulfhydryl probe, 5-iodoacetoamidofluoresceine, two free sulfhydryls of apoB-100 on LDL were identified at positions 3734 and 4190. Based on its differential susceptibility to trypsin, apoB-100 can be divided into five domains: domain 1 (residues 1-1000), largely trypsin-releasable (TR); domain 2 (residues 1001-1700), alternating TR and trypsin non-releasable (TN); domain 3 (residues 1701-3070), largely TN; domain 4 (residues 3071-4100), mainly TR and mixed; and domain 5 (residues 4101-4536), almost exclusively TN. Based on our data, we propose that the structure of apoB-100 in LDL is probably an elongated form that wraps around the LDL particle, and that Cys3734 of apoB-100 may be the cysteine residue linked to a cysteine of apo[a].

Micronucleus formation induced by three polycyclic aromatic hydrocarbons in rat bone marrow and spleen erythrocytes following intratracheal instillation.

Benz[a]anthracene (BA), dibenz[a,h]anthracene (DBA) and dibenzo[a,i]pyrene (DBP) are polycyclic aromatic hydrocarbons (PAHs) found in incomplete combustion products of fossil fuels, coal tar, and other organic materials. Workers in related industries may be exposed to these chemicals by inhalation. The information related to the potential health hazards of these chemicals to the exposed workers, however, is very limited. In the present study, micronucleus (MN) formation in rat bone marrow and spleen polychromatic erythrocytes (PCEs) was determined following three intratracheal instillations within a 24-h period with either BA, DBA or DBP. Three doses with five rats per dose were used for each chemical. Bone marrow and spleen cells were harvested 24 h after the first dosing. Results showed that the order of toxicity for the three PAHs was DBP > DBA > BA. BA induced MN in a dose-related manner in both bone marrow and spleen PCEs at doses above 25 mg/kg. DBA caused significant increases in the frequencies of MN in both spleen and bone marrow PCEs at the dose of 8.5 mg/kg or higher. At 10 mg/kg, DBP significantly increased MN frequency in spleen PCEs, but the increase in bone marrow PCEs was not significantly different from the control. These results indicate that: (1) all three PAHs studied are absorbed through the respiratory tract and their genotoxic metabolites reach the bone marrow and/or spleen; (2) except for DBP which does not induce MN in the bone marrow, all three PAHs induced MN in both bone marrow and spleen PCEs; and (3) the sensitivity of the spleen to the three PAHs is comparable to or higher than that of the bone marrow.

The in vitro micronucleus assay for detection of cytogenetic effects induced by mutagen-carcinogens: comparison with the in vitro sister-chromatid exchange assay.

The sensitivity of a cytogenetic assay, as expressed by the in vitro induction of micronuclei (MN), was compared to the in vitro induction of sister-chromatid exchanges (SCEs). Chinese hamster lung (V79) cells were exposed to 3 known alkylating agents: methyl methanesulphonate (MMS), ethyl methanesulphonate (EMS) and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and to 5 newly synthesized naphthofurans: 2-nitro-7-methoxynaphtho[2,1-b]furan (A), 2-nitro-8-methoxynaphtho[2,1-b]furan (B), 2-nitronaphtho[2,1-b]furan (C), 2-nitro-7-bromonaphtho[2,1-b]furan (D) and 7-methoxynaphtho[2,1-b]furan (E). The induction of MN only was also analysed after exposure of the cells to 4 alcohols: ethanol, methanol, butanol and propanol. The lowest dose at which a significant effect could be observed was determined. In both assays, MNNG, MMS and EMS were equally active with the following order of potency: MNNG greater than MMS greater than EMS, the latter being a very weak inducer of MN and SCE. Compounds A and B were also very effective in both assays. Compound C was a more active inducer of SCE than MN. Compounds D and E were not active in either assay. None of the 4 alcohols induced MN. Our results are compared with the previously published data on in vitro and in vivo induction of SCE and MN. We conclude that the MN in vitro assay which detects clastogens as well as agents affecting the spindle apparatus, is a good indicator of genotoxicity, though slightly less sensitive than the in vitro SCE test. It could provide a rapid, simple and inexpensive complementary short-term test for the evaluation of potentially mutagenic chemicals.

Induction of micronuclei in BALB/c-3T3 cells by selected chemicals and complex mixtures.

The genotoxicity of benzo[a]pyrene, cyclophosphamide, 2-aminoanthracene, 2-nitrofluorene, nitrosated coal-dust extracts, and cigarette-smoke condensate were tested with the micronucleus assay using an established mammalian cell line. The results showed that all chemicals and complex mixtures studied induced micronuclei in BALB/c-3T3 cells. These results indicate that BALB/c-3T3 cells are capable of activating certain promutagens and procarcinogens. It seems, therefore, that in addition to cell transformation, the micronucleus assay in BALB/c-3T3 cells without an exogenous activation system may be useful for in vitro studies to detect genotoxic chemicals and complex mixtures.

Genotoxicity of vanadium pentoxide in Chinese hamster V79 cells.

Workers in many mining and manufacturing industries are potentially exposed to vanadium. Inhalation of dust containing vanadium pentoxide (V2O5), a pentavalent compound of vanadium, has been reported to cause lung diseases. Information related to the genotoxicity and potential carcinogenicity of V2O5, however, is still limited. In this study, the effect of V2O5 on mitosis, sister-chromatid exchange (SCE), micronucleus formation (MN), and gene mutation in Chinese hamster V79 cells was determined. Cells were treated with varying concentrations of V2O5 for 24 h. The results showed that no significant increases in the frequencies of SCE or gene mutation occurred in V2O5-treated cultures. However, dose-related increases were noted for micronucleated cells in cultures exposed to this compound, and the number of binucleated cells in the presence of cytochalasin B was found to decrease with increasing V2O5 concentrations. Since the micronucleated cells induced by V2O5 contained kinetochore-positive micronuclei, their induction appears to be due to damage to the spindle apparatus. These results indicate that V2O5 is cytotoxic and aneuploidogenic to V79 cells.

The influence of the extent of target organs on sensitivities of methods for screening rodent carcinogens.

Two hundred and thirty-three rodent carcinogens from the Carcinogenic Potency Database (CPDB) were analyzed with CASE (Computer Automated Structure Evaluation), and a comparison of the extents of target organs with the sensitivities for long-term carcinogenic bioassays in rats and mice, Salmonella assay (Sty), electrophilic substructure alert analysis (ESAA) and CASE was made. The carcinogenicity of 233 chemicals was evaluated in both rat and mouse bioassays. The present study showed that the sensitivities of the five methods for screening carcinogens were related to the extents of target organs of carcinogens. Among the carcinogens that did not induce tumors (extent = 0) in rats, the sensitivities of Sty and ESAA were 46 and 53, respectively. Among the carcinogens which induced tumors at a single organ (extent = 1) in rats, the sensitivities were 57 and 64 respectively; and 71 and 80 at multiple organs (extent > 1) respectively. The sensitivities of CASE were 76, 82, and 89 respectively at these three different extents. Similar results were obtained with these carcinogens in mice. The results indicate that mutagenic or electrophilic carcinogens are more likely to induce tumors at multiple target organs; in contrast, most carcinogens which induced tumors at only a single target organ in one species are rarely mutagenic or electrophilic. The sensitivities of Sty and ESAA were lower than that of the CASE method in these carcinogens. CASE analyzed chemical structures of many carcinogens and non-carcinogens and then established a database of key fragments, and its parameters are not only based on mutagenicity or electrophilicity of chemicals, and this resulted in a more exact detection of the carcinogenicity of chemicals with the CASE method.