bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibitory effect of ascorbic acid post‐treatment on radiation‐induced chromosomal damage in human lymphocytes in vitro
Authors: Konopacka Maria , Palyvoda Olena , Rzeszowska‐Wolny Joanna 
Published: October 2002

AbstractIn the present study, the effect of exposure to ascorbic acid (vitamin C) after γ‐ray‐induced chromosomal damage in cultured human lymphocytes was examined to explore the mechanism by which this antioxidant vitamin protects irradiated cells Non‐irradiated lymphocytes were exposed to increasing concentrations of ascorbic acid (1–100 μg/ml) and DNA damage was estimated using chromosomal aberration analysis and the comet assay. The results showed that ascorbic acid did not influence the frequency of chromosomal aberrations in non‐irradiated cells, except at the highest concentration (20 μg/ml), which induced breakage‐type chromosomal aberrations. Vitamin C at the concentration of 50 μg/ml caused DNA damage detected by the comet assay. A significant (34%) decrease in the frequency of chromosomal aberrations was observed in lymphocytes exposed to γ‐radiation and then cultured in the presence of ascorbic acid (1 μg/ml). The removal of DNA breaks in cells exposed to 2 Gy of γ‐radiation was accelerated in the presence of ascorbic acid as determined by the comet assay, suggesting that it may stimulate DNA repair processes. Teratogenesis Carcinog. Mutagen. 22:443–450, 2002. © 2002 Wiley‐Liss. Inc.
Evaluation of the aneugenic potential of the fungicide Ferbam in mice
Authors: Shanthi R. , Krishnamoorthy M. 
Published: October 2002

AbstractFerbam, a potent dithiocarbamate fungicide is used as a protectant against a wide variety of fungal diseases in fruits, vegetables, and ornamental plants. The wide‐spread use of this chemical is likely to pollute the environment. Hence, it was planned to test the possible genotoxicity of Ferbam through its aneugenic potential in the in vivo mouse (Mus musculus) test system. Four different doses of Ferbam, namely, 7.5, 15.0, 30.0, 60.0 mg/kg body weight were administered orally to mice Mus musculus suspended in gum tragacanth representing, respectively, 1/16, 1/8, 1/4;, 1/2th of the LD50 value. They were sacrificed at 6‐, 12‐, 24‐, and 48‐h intervals along with a distilled water negative control at 2 mg/kg body weight. Colchicine treated animals were used as positive controls. Bone marrow preparations were made following the standard Hypotonic flame dry Giemsa staining technique to study the dose and time yield effect of Ferbam. The aneugenic potential was evaluated for C‐mitotic effects by scoring the mitotic index, c‐mitoses frequency, anaphase reduction, and hyper/hypodiploidy induction. Ferbam showed a significant increase in the mitotic index and C‐mitoses effects and anaphase decreased at the highest doses of 30 and 60 mg/kg at 12‐ and 24‐h intervals. Colchicine induced significant effects in all the aneugenic parameters observed at all the time intervals. There was no significant induction of either hyperdiploidy or hypodiploidy by Ferbam, unlike colchicine, indicating that the fungicide Ferbam is not aneugenic in the mouse test system. Teratogenesis Carcinog. Mutagen. 22:451–459, 2002. © 2002 Wiley‐Liss, Inc.
Effects of chlorophyllin on mouse embryonic and fetal development in vivo
Authors: García‐Rodríguez Ma. Carmen , Morales‐Ramírez Pedro , Altamirano‐Lozano Mario 
Published: October 2002

AbstractChlorophyllin (CHL) has proven that there is antimutagenic and anticarcinogenic activity in several organisms without causing lethal effects. However, there is no information about its effects when it is administered in gestation. In the present study, we assessed possible effects of CHL when it was administered to CD‐1 mice on the 8th day of gestation using the same doses and administration route used in ours previous antimutagenic and antigenotoxic studies. Females were exposed to a single dose of CHL by i.p. injection (20, 40, 50, or 100mg/kg b.w.). On day 18 all dams were subjected to cesarean section and the fetuses were examined with common teratological methods. Results show that CHL‐treatment induced total litter loss and is dose‐dependent, probably due to either the interaction between CHL and some general control mechanisms of embryo development or by an impairment of maternal‐fetal interactions. The analysis of uterine horns of the CHL‐treated females with total litter loss revealed the presence of green rings in the uterus. Results show the inverse relationship between the number of live implants and the frequency of green rings, indicating implantation sites where embryo death and early resorptions occurred. Although CHL was given in a single dose on day 8 in this study, the results indicate that CHL is associated with significant embryo lethality. Teratogenesis Carcinog. Mutagen. 22:461–471, 2002. © 2002 Wiley‐Liss, Inc.
Implantation of MNNG crystals into a Triturus intact limb affects mitotic and labeling indices, regeneration rate, and morphogenesis in the contralateral, regenerating limb
Authors: Keramitsoglou T. , Grispou E. , Margaritis L.H. , Koussoulakos S. 
Published: October 2002

AbstractExperimental administration of chemical carcinogens to various mammals is highly effective in inducing malignant tumors. In contrast, treatment of regeneration‐competent animals even with much higher doses of the same drugs only exceptionally leads to tumor‐like growth. Usually, carcinogenic materials implanted or injected into a regenerating limb of urodele amphibia interfere with the regenerative process and frequently lead a) to growth retardation or arrest of regeneration, b) to development of a great variety of abnormal regenerates, and c) to generation of accessory, limb‐like structures. Autonomous or experimental incidence of carcinogenesis is extremely low in animals endowed with strong regenerative capabilities. Of exceptional biological significance is the fact that such induced tumors usually regress spontaneously. This unique property of the regeneration‐competent animals to resist carcinogenesis provides opportunities to compare non‐cancerous alterations in the differentiated state of adult cells to those occurring in neoplasia. The mode of action of the chemical carcinogens on limb regeneration has not yet been clarified with certainty at the cellular and the molecular level. Several scientists claim that the above‐mentioned effects might be attributed to local toxic influences of the drugs; therefore the present study was designed to investigate whether the administration of the carcinogen MNNG can affect cell proliferation, histogenesis, and morphogenesis at a region distant from the site of its implantation, even after a relatively long time period. To this end, 40 animals of the species Triturus cristatus had their right hindlimb surgically removed at the distal zeugopod. Then, a small microcrystal (approximately 5 µg) of MNNG was inserted under the ventral aspect of the skin of the left tarsus in 20 of these animals (groups T and A; see below). Two months later, nine of the MNNG‐treated animals were injected intraperitoneally with tritiated thymidine. After 2 h, six of these animals had their right hindlimb amputated at the distal zeugopod, whereas the rest were left to regenerate. The results were evaluated by camera lucida drawings, clearing in methyl benzoate, classical histology, and autoradiography. It was revealed that administration of MNNG at a somatic region (left hindlimb) reduces DNA synthesis and mitosis at a distant place (right hindlimb) even 2 months after MNNG implantation. Despite this, the rate of limb elongation is not substantially reduced. Classical histology revealed normal tissue structure throughout. All regenerated limbs displayed several teratogenic abnormalities. Teratogenesis Carcinog. Mutagen. 22:473–483, 2002. © 2002 Wiley‐Liss, Inc.
Identification of polymorphisms in the human Reprimo gene using public EST data
Authors: Ye Zheng , Parry James M. 
Published: October 2002

AbstractThe human Reprimo gene is a recently identified cytoplasmic protein, which plays an important role in the regulation of p53‐dependent G2 arrest of the cell cycle. Genetic variations in the Reprimo gene that may influence enzyme activity can be of both biological and epidemiological significance. The human expressed sequence tag (EST) database is a wealth of resources, which can be used to rapidly screen for potential polymorphisms in proteins of physiological interest. On the basis of the alignment of human EST sequences, we identified two candidate polymorphisms at nucleotides 824 and 839 in the 3′‐untranslated region of the Reprimo gene. The presence of these polymorphisms was confirmed in a Caucasian population (n=82) by the use of the allele specific polymerase chain reaction (PCR). The rare allele frequency at position 824 (38.4%) is much higher than rare allele frequency at position 839 (3.7%). Our results suggest that the human EST data may serve as a valuable source for the rapid identification of genetic variation. Teratogenesis Carcinog. Mutagen. 22:485–493, 2002. © 2002 Wiley‐Liss, Inc.
Birth order and oral clefts: A meta analysis
Authors: Vieira Alexandre R. , Orioli Iêda M. 
Published: October 2002

AbstractBackgroundThere is evidence that late birth order is associated with some complex disorders. For orofacial clefts there is no consensus as to whether increased birth order is associated or not. A meta‐analysis of published data on cleft lip or cleft palate (CL/P and CP) was carried out to ascertain whether there is an increased risk for children of high birth order to have an oral cleft.MethodsAll data available with information regarding the frequency of live births and CL/P and CP cases by birth order (1, 2, 3, and 4 or more) were included in the analysis, and the birth order category “1” was considered to be with no risk (OR = 1.0).ResultsChildren with higher birth order are more likely to have CL/P and CP with odds ratios increasing with birth order to a peak of 3.0 in children birth order “4 or more.” Results are not different when isolated and syndromic cases are combined.ConclusionsCL/P and CP occurrence is correlated with increasing birth order. Further studies, taking into consideration sample size and factors such as income status, race, paternal age, vitamin intake, and social habits, should be done to determine conclusively the association between birth order and oral clefts. Teratology 66:209–216, 2002. © 2002 Wiley‐Liss, Inc.
Orofacial clefts and spina bifida: N‐Acetyltransferase phenotype, maternal smoking, and medication use
Authors: Van Rooij Iris A.L.M. , Groenen Pascal M.W. , Van Drongelen Merel , Te Morsche René H.M. , Peters Wilbert H.M. , Steegers‐Theunissen Régine P.M. 
Published: October 2002

AbstractBackgroundOrofacial clefts and spina bifida are midline defects with a multifactorial etiology. Maternal smoking and medication use periconceptionally have been studied as risk factors for these malformations. The biotransformation enzyme N‐acetyltransferase 2 (NAT2), plays a part in the inactivation of toxic compounds in cigarette smoke and medication. We investigated maternal NAT2 phenotype and the interaction with smoking and medication use periconceptionally on orofacial cleft and spina bifida risk in offspring.MethodsIn this case‐control study of 45 mothers of orofacial cleft children, 39 mothers of spina bifida children and 73 control mothers, NAT2 acetylator status was determined by measuring urinary caffeine metabolites.ResultsSlow NAT2 acetylators showed no increased risk for orofacial cleft (OR = 1.0, 95% CI: 0.4–2.3) or spina bifida offspring (OR = 0.7, 95% CI: 0.3–1.7) compared to fast NAT2 acetylators. More mothers with orofacial cleft and spina bifida offspring smoked cigarettes (36% and 23% respectively) and used medication periconceptionally (38% and 44% respectively) compared to control mothers (smoking:18%, medication use:19%). No interaction between maternal NAT2 acetylator status and smoking or medication use was observed for orofacial cleft and spina bifida risk.ConclusionsMaternal smoking and medication use is associated with orofacial cleft risk as well as medication use is with spina bifida. The maternal NAT2 acetylator status, however, was not associated with an increased risk for orofacial cleft or spina bifida offspring, nor in combination with periconceptional smoking or medication use. Teratology 66:260–266, 2002. © 2002 Wiley‐Liss, Inc.
Methylmercury distribution in the pregnant rat and embryo during early midbrain organogenesis
Authors: Lewandowski T.A. , Pierce C.H. , Pingree S.D. , Hong S. , Faustman E.M. 
Published: October 2002

AbstractBackgroundThe period of neurogenesis represents a window of susceptibility for in utero methylmercury (MeHg) exposure. This study examined the toxicokinetics of potentially neurotoxic doses of MeHg during neurogenesis in the developing rat to provide additional information in the areas of mercury speciation and inter‐study variability.MethodsPregnant Sprague‐Dawley rats were dosed s.c. with 5–22 mg/kg MeHg on Day 11 of gestation to target rapidly dividing cells of the developing midbrain. Maternal liver, kidney, skin, blood, placenta, and the embryonic body and brain were evaluated for total and inorganic mercury content at 24, 48, and 72 hr after dosing. Tissue Hg partitioning ratios derived from our data were then compared to those derived from previous studies.ResultsMercury was present in all tissues examined by 24 hr after dosing, and levels remained relatively stable over the subsequent 2 days in most tissues. The exceptions were the maternal blood and kidney, in which total mercury decreased significantly over the three days after dosing. Inorganic mercury concentrations were similarly stable over time. At maternal MeHg doses above 12 mg/kg, non‐linearities were observed in mercury accumulation in the embryo, placenta and maternal liver. The mercury tissue partitioning coefficients ranged from 0.09 for maternal blood:embryo to 1.97 for maternal blood:kidney.ConclusionsOur observations at the 5 mg/kg dose were consistent with those of previous studies that involved evaluations at slightly later gestational times. The estimates of tissue partitioning coefficients we derived using multiple studies provide valuable insight into the effects of inter‐study variability. Teratology 66:235–241, 2002. © 2002 Wiley‐Liss, Inc.
Risk factors for heart disease associated with abnormal sidedness
Authors: Kuehl Karen S. , Loffredo Christopher 
Published: October 2002

AbstractBackgroundThe purpose of this study is to obtain information on potential familial and environmental risk factors for liveborn cases of heart disease associated with abnormal visceral and vascular sidedness, heterotaxy heart disease, so that hypotheses about this congenital cardiovascular malformation (CCVM) and its risk factors can be generated. We describe the characteristics of infants with heterotaxy heart malformations and case‐control comparisons of interview data obtained on parental socio‐demographic characteristics, occupational and household environmental exposures.MethodsCases and controls are drawn from the Baltimore Washington Infant Study (BWIS) a population based case control study of CCVM diagnosed in the region from 1981–89.ResultsMaternal diabetes (OR = 5.5, 95% CI = 1.6–19.1) and family history of malformations (OR = 5.1, 95% CI = 2.0–12.9) are strongly associated with cardiac disorders of sidedness. Cocaine use by mothers during the first trimester is associated with heterotaxy heart disease with odds of 3.7 (95% CI = 1.3–10.7). Cases of isolated dextrocardia shared risk factors with other heterotaxy malformations. The odds of a twin proband having heterotaxy heart disease is 4.8 (95% CI = 1.9–11.8) compared to singleton births. Twin probands are predominantly monozygotic twins in contrast to twin probands in other congenital cardiovascular malformations.ConclusionsOur findings are consistent with a role for multiple genetic factors in the development of left‐right axis formation and with variable cardiac phenotypes according to gene expression and possible gene‐environment interactions. Association with monozygotic twinning and with parental cocaine use may point to additional mechanistic clues for future research. Teratology 66:242–248, 2002. © 2002 Wiley‐Liss, Inc.
13C‐NMR study of hypoglycemia‐induced glycolytic changes in embryonic mouse heart
Authors: Ghatnekar Gautam S. , Gracz Hanna S. , Smoak Ida W. 
Published: October 2002

AbstractBackgroundGlucose metabolites can be detected in embryonic mouse tissues using 13C‐NMR spectroscopy. The advantage of this method is in its chemical specificity and the ability to follow metabolic changes.MethodsIn this study, CD‐1 mice were mated and embryos excised on gestational day (GD) 10.5 (plug = GD 0.5). Hearts were isolated and cultured in 150 mg/dl glucose (normoglycemic medium) or 40 mg/dl glucose (hypoglycemic medium) for 6 hr. 13C‐labeled glucose comprised 62%–64% of total glucose in the culture medium. Pre‐ and postculture media were treated with deuterated water (D2O), and 13C spectra were obtained using a Bruker Avance 500 MHz spectrometer operating at 11.744 tesla (125.7 MHz for 13C). NMR spectra demonstrated resonances for 13C‐glucose in preculture normoglycemic and hypoglycemic media. Postculture spectra for normoglycemic and hypoglycemic media demonstrated 13C‐glucose signals as well as a signal for 13C‐lactate. Area under the curve (AUC) was measured for the [1‐13C‐glucose] resonance from preculture media and the [3‐13C‐lactate] resonance from postculture media. The ratios of AUC for postculture [3‐13C‐lactate] to preculture [1‐13C‐glucose] were calculated and found to be higher in hypoglycemic than in normoglycemic media.ResultsOur results confirm earlier findings using radiolabeled substrates and suggest that 13C‐NMR spectroscopy can be used to study glucose metabolism in isolated embryonic hearts exposed to hypoglycemia.ConclusionsNMR effectively measures glucose and its metabolite, lactate, in the same spectrum and thus determines metabolic flux in the isolated embryonic heart after exposure to hypoglycemia and normoglycemia. This method could evaluate glucose metabolism in embryonic tissues following other teratogenic exposures. Teratology 66:267–272, 2002. © 2002 Wiley‐Liss, Inc.
Numerical Simulations of Fractionated Electrograms and Pathological Cardiac Action Potential
Authors: Sanfelici Simona 
Published: October 2002

The aim of this work is twofold. First we focus on the complex phenomenon of electrogram fractionation, due to the presence of discontinuities in the conduction properties of the cardiac tissue in a bidomain model. Numerical simulations of paced activation may help to understand the role of the membrane ionic currents and of the changes in cellular coupling in the formation of conduction blocks and fractionation of the electrogram waveform. In particular, we show that fractionation is independent of INA alterations and that it can be described by the bidomain model of cardiac tissue. Moreover, some deflections in fractionated electrograms may give nonlocal information about the shape of damaged areas, also revealing the presence of inhomogeneities in the intracellular conductivity of the medium at a distance.The second point of interest is the analysis of the effects of space–time discretization on numerical results, especially during slow conduction in damaged cardiac tissue. Indeed, large discretization steps can induce numerical artifacts such as slowing down of conduction velocity, alteration in extracellular and transmembrane potential waveforms or conduction blocks, which are not predicted by the continuous bidomain model. Several possible numerical and physiological explanations of these effects are given. Essentially, the discrete system obtained at the end of the approximation process may be interpreted as a discrete model of the cardiac tissue made up of isopotential cells where the effective intracellular conductivity tensor depends on the space discretization steps; the increase of these steps results in an increase of the effective intracellular resistance and can induce conduction blocks if a certain critical value is exceeded.
A DNA Methyltransferase Can Protect the Genome from Postdisturbance Attack by a Restriction-Modification Gene Complex
Authors: Takahashi Noriko , Naito Yasuhiro , Handa Naofumi , Kobayashi Ichizo 
Published: October 2002

ABSTRACT

In prokaryotic genomes, some DNA methyltransferases form a restriction-modification gene complex, but some others are present by themselves. Dcm gene product, one of these orphan methyltransferases found in
Escherichia coli
and related bacteria, methylates DNA to generate 5′-C
m
CWGG just as some of its eukaryotic homologues do. Vsr mismatch repair function of an adjacent gene prevents C-to-T mutagenesis enhanced by this methylation but promotes other types of mutation and likely has affected genome evolution. The reason for the existence of the
dcm
-
vsr
gene pair has been unclear. Earlier we found that several restriction-modification gene complexes behave selfishly in that their loss from a cell leads to cell killing through restriction attack on the genome. There is also increasing evidence for their potential mobility.
Eco
RII restriction-modification gene complex recognizes the same sequence as Dcm, and its methyltransferase is phylogenetically related to Dcm. In the present work, we found that stabilization of maintenance of a plasmid by linkage of
Eco
RII gene complex, likely through postsegregational cell killing, is diminished by
dcm
function. Disturbance of
Eco
RII restriction-modification gene complex led to extensive chromosome degradation and severe loss of cell viability. This cell killing was partially suppressed by chromosomal
dcm
and completely abolished by
dcm
expressed from a plasmid. Dcm, therefore, can play the role of a “molecular vaccine” by defending the genome against parasitism by a restriction-modification gene complex.
Metabolic Flux in Both the Purine Mononucleotide and Histidine Biosynthetic Pathways Can Influence Synthesis of the Hydroxymethyl Pyrimidine Moiety of Thiamine in
Salmonella enterica
Authors: Allen Shara , Zilles Julie L. , Downs Diana M. 
Published: October 2002

ABSTRACT

Together, the biosyntheses of histidine, purines, and thiamine pyrophosphate (TPP) contain examples of convergent, divergent, and regulatory pathway integration. Mutations in two purine biosynthetic genes (
purI
and
purH
) affect TPP biosynthesis due to flux through the purine and histidine pathways. The molecular genetic characterization of
purI
mutants and their respective pseudorevertants resulted in the conclusion that <1% of the wild-type activity of the PurI enzyme was sufficient for thiamine but not for purine synthesis. The respective pseudorevertants were found to be informational suppressors. In addition, it was shown that accumulation of the purine intermediate aminoimidazole carboxamide ribotide inhibits thiamine synthesis, specifically affecting the conversion of aminoimidazole ribotide to hydroxymethyl pyrimidine.