Inhibitory effect of folinic acid on radiation-induced micronuclei and chromosomal aberrations in V79 cells

Folinic acid (FA), clinically called leucovorin, has been widely used as a nutrient supplement in dietary intake and is capable of inhibiting cytotoxicity and chromosomal damage induced by chemicals. However, data on its antigenotoxic effect on radiation-induced chromosomal damage are limited. The present study was, therefore, performed to investigate the effect of FA on radiation-induced (X-rays and UV radiation) micronuclei (MN) and structural chromosomal aberrations (SCA) concurrently in V79 Chinese hamster lung cells. Exponentially growing cells were exposed to five doses of X-rays (1-12 Gy) and UV radiation (50-800 microJ x 10(2)/cm2) and post-treated with 5 or 50 micrograms FA/ml of culture medium for 16 h. The slides were analyzed for the presence of MN and SCA using standard procedures. The results showed that X-ray treatment alone produced dose-related cytotoxicity as measured by nuclear division index (NDI) and mitotic index (MI). X-rays produced a clear dose-related clastogenicity as measured by percent of micronucleated binucleated cells (MNBN) (5-79%) and percent of aberrant cells (11-92%). FA at 5 micrograms/ml slightly decreased X-ray induced chromosomal damage in both assays; however, the inhibition was significant (12-46% of MNBN, 14-48% in aberrant cells) only when X-ray-treated cultures were post-treated with 50 micrograms FA/ml. Post-treatment of FA had no effect on X-ray induced cytotoxicity as measured by NDI and MI. A similar a dose-related increase in % MNBN (0.5-10.3%) and percent aberrant cells (6-35%) was produced by UV radiation treatment alone. There were significant percentages of MNBN and aberrant cell inhibitions at both 5 and 50 micrograms/ml in both assays. As in the case of X-ray-treated cells, there was a clear dose-related cytotoxicity in UV-treated cells alone. No reduction in NDI or MI was found when UV-exposed cells were post-treated with 5 or 50 micrograms of FA. These data demonstrate the beneficial effect of FA in decreasing radiation-induced chromosomal damage.     

Response of V79 cells to low doses of X-rays and negative pi-mesons: clonogenic survival and DNA strand breaks

Mammalian cells are hypersensitive to very low doses of X-rays (< 0.2 Gy), a response which is followed by increased radioresistance up to 1 Gy. Increased radioresistance is postulated to be a response to DNA damage, possibly single-strand breaks, and it appears to be a characteristic of low linear energy transfer (LET) radiation. Here we demonstrate a correspondence between the extent of the increased radioresistance and linear energy transfer of 250 kVp X-rays and plateau and Bragg peak negative pi-mesons. The results support our hypothesis since the size of the increased radioresistant response appears to correspond to the number of radiation induced single-strand breaks. Furthermore, since survival prior to the increased radioresistant response (< 0.2 Gy) was LET-independent, these data support the notion that the increased radioresistant response may dictate the overall survival response to higher doses. However, while these data provide further circumstantial evidence for the involvement of DNA strand breaks in the triggering of increased radioresistance, more direct conclusions cannot be made. The data are not accurate enough to detect structure in the single-strand break profiles, the production of single-strand breaks being apparently linear with dose.     

Increased DNA oxidation and decreased levels of repair products in Alzheimer's disease ventricular CSF

One of the leading etiologic hypotheses regarding Alzheimer's disease (AD) is the involvement of free radical-mediated oxidative stress in neuronal degeneration. Although several recent studies show an increase in levels of brain DNA oxidation in both aging and AD, there have been no studies of levels of markers of DNA oxidation in ventricular CSF. This is a study of levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG), the predominant marker of oxidative DNA damage, in intact DNA and as the "free" repair product that results from repair mechanisms. Free 8-OHdG was isolated from CSF from nine AD and five age-matched control subjects using solid-phase extraction columns and measured using gas chromatography/mass spectrometry with selective ion monitoring. Intact DNA was isolated from the same samples and the levels of 8-OHdG determined in the intact structures. Quantification of results was carried out using stable isotope-labeled 8-OHdG. By using this sensitive methodology, statistically significant elevations (p < 0.05) of 8-OHdG were observed in intact DNA in AD subjects compared with age-matched control subjects. In contrast, levels of free 8-OHdG, removed via repair mechanisms, were depleted significantly in AD samples (p < 0.05). Our results demonstrate an increase in unrepaired oxygen radical-mediated damage in AD DNA as evidenced by the increased presence of 8-OHdG in intact DNA and decreased concentrations of the free repair product. These data suggest that the brain in AD may be subject to the double insult of increased oxidative stress, as well as deficiencies in repair mechanisms responsible for removal of oxidized bases.     

Review of Psychology in Relation to Medicine (Second edition).

Reviews the book, Psychology in Relation to Medicine (Second edition) by R. M. Mowbray and T. Ferguson Rodger. Until the relationships between psychology and medicine become less ambiguous than they are at present, books such as this are both difficult to write and difficult to review. The relationships between these two professions may be viewed in many ways, but there are two broad views prevalent. The first view sees psychology as one of the basic sciences of medicine--a basic science that is particularly relevant in the training of psychiatrists. The other view sees psychology as a discipline that runs parallel to medicine. If one were to accept the first of these views, then presumably the medical student would be required to obtain a thorough grounding in psychology. If one takes the second view of the relationship between psychology and medicine, then the medical student requires probably only one course which will give him some familiarity with the work one of his close professional colleagues will be doing. The reviewer suggests that satisfactory books for medical students will only be written and can only be written when the relationships between psychology and medicine are more precisely delineated. Whatever these relationships may be, it is likely that the books written for medicine and accepted by the medical profession for their students will be more meaty than this one. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Relation between food and water intake in the pigeon (Columba livia).

In 4 experiments with 40 male White Carneaux pigeons, continuous monitoring of feeding and drinking activity under ad-lib conditions showed that food and water intake were closely associated temporally with 70.0% of water intake occurring just prior to, during, and immediately following a meal. There was a significant positive correlation between 24-hr food and water intake. However, the association between food and water intake varied temporally during ad-lib and food-restriction schedules. Under ad-lib conditions, there was a significant correlation between food and water intake during a 2-hr period in the morning but not the afternoon. Likewise, when food was restricted for a 2-hr period in the morning, water intake was significantly correlated with food intake. During total food deprivation, drinking was primarily confined to the light portion of the light–dark cycle. Data suggest that the amount of water ingested as well as the temporal pattern of water intake is not solely dependent on food intake and may be determined by an underlying temporal rhythm of drinking. (28 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Different effects of inorganic and dimethylated arsenic compounds on cell morphology, cytoskeletal organization, and DNA synthesis in cultured Chinese hamster V79 cells

Changes in cytoskeletal organization of cultured V79 cells exposed to arsenite and dimethylarsinic acid (DMAA), a methylated derivative of inorganic arsenics, and related changes, such as mitotic arrest and induction of multinucleated cells, were investigated in comparison with their effects on DNA synthesis. DMAA caused mitotic arrest and induction of multinucleated cells with a delay of 12 h relative to the mitotic arrest. By contrast, arsenite at equitoxic concentrations to DMAA was less effective than DMAA in causing mitotic arrest and in inducing multinucleated cells. Post-mitotic incubation of cells arrested in metaphase by 6 h incubation with 10 mM DMAA showed that the incidence of multinucleated cells increased conversely with a rapid decrease in metaphase cells. This suggests that metaphase-arrested cells can escape from metaphase, resulting in the appearance of multinucleated cells. The mitotic arrest caused by DMAA was accompanied by disruption of the microtubule network. By contrast, both arsenite and DMAA did not cause disorganization of actin stress fibers even when incubated at concentrations that caused a marked retardation of cell growth. Cells exposed to arsenite for 6 h showed marked inhibition of DNA synthesis, whereas inhibition by DMAA was not observed. When incubation was prolonged by 18 h, the arsenite-induced inhibition of DNA synthesis was mitigated. By contrast, inhibition of DNA synthesis by DMAA occurred in parallel with an increase in the population of mitotic cells. These results suggest that DMAA caused growth retardation and morphological changes via disruption of the microtubule network, and that arsenite-induced retardation of cell growth and inhibition of DNA synthesis were not attributable to the cytoskeletal changes.     

Increased 8-hydroxyguanine levels in DNA and its repair activity in rat kidney after administration of a renal carcinogen, ferric nitrilotriacetate

The renal carcinogen, ferric nitrilotriacetate (Fe-NTA), is known to induce oxidative stress and the subsequent formation of a type of oxidative DNA damage, 8-hydroxyguanine (8-OH-Gua), in the rat kidney (Umemura et al., 1990). Using an improved DNA isolation method (Nakae et al., 1995), which reduces the background level of 8-OH-Gua, we found a five-fold increase in the 8-OH-Gua level in kidney DNA after a single i.p. injection of Fe-NTA. On the basis of the report that 8-OH-Gua repair activity is enhanced after cells are exposed to oxidative stress due to ionizing radiation (Bases et al., 1992), the measurement of 8-OH-Gua repair activity will also be useful to assess cellular oxidative stress. The 8-OH-Gua repair enzyme activity was determined with an endonuclease assay using a 22 mer DNA that contains 8-OH-Gua at a specific position. A five-fold increase in the 8-OH-Gua repair activity as compared with the control, was observed in the target organ, the rat kidney, 120 h after Fe-NTA administration. In the non-target organ, the liver, the increase was not as large (two-fold). This simple assay of oxidative DNA damage repair will be useful for evaluating the carcinogenicity of oxygen radical forming chemicals, in addition to chemical analyses of oxidative DNA damage.     

Possible role of glutathione in resistance to heavy metals and hydrogen peroxide in a radioresistant Chinese hamster V79 cell strain

To understand the cellular and biochemical nature of radioresistance in the strain M5 derived from Chinese hamster V79 cells, the sensitivity of the resistant cells towards CdCl2, Zn(Ac)2, and H2O2 by the colony forming ability has been tested. D0 values for these compounds in Chinese hamster V79 cells were 5.4 microM, 27.8 microM and 4.3 micrograms/ml respectively while for M5 cells these were 8.3 microM, 142.9 microM and 11.9 micrograms/ml respectively. The resistance to heavy metals as well as the oxidative damage could be reversed by the inhibition of glutathione synthesis by the drug buthionine sulfoximine (BSO). These set of data indicate that the cellular antioxidant glutathione plays an important role in the observed oxidant-resistant phenotype as well as heavy metal resistance in M5 cells.     

Primary repair is superior to initial palliation in children with atrioventricular septal defect and tetralogy of Fallot

OBJECTIVE:The objective was to explore the best management algorithm for atrioventricular septal defect in conjunction with tetralogy of Fallot. METHODS: We reviewed the cases of 38 children referred to our division (March 1981-August 1997) who had atrioventricular septal defect associated with tetralogy of Fallot; 32 (84%) had Down syndrome. Twenty-one received initial palliation with a systemic-to-pulmonary artery shunt; of these, 2 (9.5%) died before complete repair. Thirty-one children underwent complete repair; 14 of these (45%) had undergone initial palliation (mean age at shunt 20 +/- 24 months). Right ventricular outflow obstruction was relieved by a transannular patch in 22 (71%); 14 (64% of 22) had a monocuspid valve inserted. Four required an infundibular patch. RESULTS: Two children (6.4%) died early after repair; 1 had undergone previous palliation. Patients with palliation underwent repair at an older age (78 vs 36 months), required longer ventilatory support (8 vs 4 days) and inotropic support (8 vs 4 days), and had longer intensive care stays (11 vs 6 days) and hospital stays (24 vs 15 days). Eleven children (35%) underwent reoperation, 7 (58%) for right ventricular outflow reconstruction and pulmonary arterioplasty. Reoperation was more frequent in the palliation group than in the primary operation group (64% vs 12%). The single late death was related to a reoperation in the palliation group. CONCLUSIONS: Atrioventricular septal defect with tetralogy of Fallot can be repaired with a low mortality rate. Initial palliation with a shunt resulted in a more complex postoperative course and a higher reoperative rate. Primary repair is superior to initial palliation with later repair.     

Relation between food preference and food-elicited vocalizations in golden lion tamarins (Leontopithecus rosalia).

Reports the results of 2 studies on food-elicited vocalizations in golden lion tamarins. First, the preferences of 10 golden lion tamarins for 6 foods were investigated. Tamarins prefer mealworms and raisins significantly more than apple, egg, carrot, or marmoset diet. Food preference rank was significantly and positively correlated with the rank of latency to choose a particular food. Second, the relation between food preference and 15 vocal parameters measured from the calls emitted by 5 tamarins to a subset of the foods was investigated. Only 1 parameter was significantly correlated with food preference across animals. Within-Ss multivariate analysis of variance (ANOVA) showed that the vocalizations to foods are significantly different. Results support a hypothesis that food-elicited vocalizations vary in ways that correspond to the caller's preference but not in a manner that labels food type. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Mexican Americans' initial preferences for counselors: Research methodologies or researchers' values? Reply to Atkinson and Wampold (1993).

D. R. Atkinson and B. E. Wampold's (see record 1993-26416-001) assessment of the available methods to study counselor preference failed to consider the limitations of the judgment and multidimensional approaches and the strength of the single-dimension choice approach, the method used by S. R. López et al (see record 1992-06260-001) in their research. In recognizing that each method has its respective strengths and weaknesses, it is important that researchers use multiple methods to assess counselor preferences. Naturalistic studies of counseling will ultimately determine which method or methods are most valid. It is suggested that the emphasis placed on a given method and the interpretation of given findings may reflect the degree to which researchers value the role of ethnicity and culture in counseling. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The belief bias effect is aptly named: A reply to Klauer and Kellen (2011).

In “Assessing the Belief Bias Effect With ROCs: It's a Response Bias Effect,” Dube, Rotello, and Heit (see record 2010-14834-005) examined the form of receiver operating characteristic (ROC) curves for reasoning and the effects of belief bias on measurement indices that differ in whether they imply a curved or linear ROC function. We concluded that the ROC data are in fact curved and that analyses using statistics that assume a linear ROC are likely to produce Type I errors. Importantly, we showed that the interaction between logic and belief that has inspired much of the theoretical work on belief bias is in fact an error stemming from inappropriate reliance on a contrast (hit rate?false alarm rate) that implies linear ROCs. Dube et al. advanced a new model of belief bias, which, in light of their data, is currently the only plausible account of the effect. Klauer and Kellen (2011) disputed these conclusions, largely on the basis of speculation about the data collection method used by Dube et al. to construct the ROCs. New data and model-based analyses are presented that refute the speculations made by Klauer and Kellen. We also show that new modeling results presented by Klauer and Kellen actually support the conclusions advanced by Dube et al. Together, these data show that the methods used by Dube et al. are valid and that the belief bias effect is simply a response bias effect. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Detection of telomerase activity in Chinese hamster V79 cells and its inhibition by 7-deaza-deoxy guanosine triphosphate and (TTAGGG)4 in vitro

To investigate the nature of telomerase activity and its inhibition in Chinese hamster V79 cells, we have detected telomerase activity in Chinese hamster cells using Telomeric Repeat Amplification Protocol (TRAP) assay. We have further studied inhibition characteristics of this enzyme in vitro by nucleotide analogue 7-deaza-2'-deoxy guanosine triphosphate (7-deaza-dGTP) and oligonucleotide (TTAGGG)4. Both the inhibitors inhibited the telomerase activity in a dose dependent manner. To attain 50% inhibition of the telomerase activity, we needed about 4.5 microM of 7-deaza-dGTP. Similarly, preincubation at 37 degreesC of the cell extract with 1.25 x 10(-3) microgram oligonucleotide (TTAGGG)4 showed 50% inhibition of the control value. Inhibition of telomerase activity by 7-deaza-dGTP could be due to the incorporation of the modified nucleotide in the telomeric repeat and thus altering the further binding/extension by the enzyme. (TTAGGG)4 could have possibly interacted with RNA component of telomerase and inhibited its activity.     

Gene stability in transgenic aspen (Populus). I. Flanking DNA sequences and T-DNA structure

The stability of transgenes in the genome of transformed plants depends strongly on their correct physical integration into the host genome as well as on flanking target DNA sequences. For long-lived species like trees, however, no information is available so far concerning inactivation or loss of transgenes due to gene silencing or somatic genome rearrangement events. In this study, four independently transformed 35S-rolC transgenic hybrid aspen plants (Populus tremula L. x tremuloides Michx.), each harbouring one copy of the transgene, were investigated during continuous growth in the greenhouse. In one of these transgenic lines (Esch5:35S-rolC-#1) individuals frequently show phenotypic reversions, while in the remaining three lines (Esch5:35S-rolC-#3, -#5, -#16) the gene was essentially stable. Molecular analysis including PCR, Southern and Northern assays clearly showed that the transgene had been lost in the revertant tissue of the unstable line. Sequencing of T-DNA right and left borders, and flanking DNA regions, in all four transgenic aspen lines revealed no differences either in the type of flanking DNA (G-C to A-T ratio) or with respect to the presence of enhancers or MAR (matrix associated repeats)-like structures. Primers located within the left and right flanking regions in the three stable lines could be used to recover the target sites from the untransformed plants. This was not possible, however, with the unstable line, indicating that at least one flanking sequence does not derive from the plant target DNA but is of unknown origin. PCR using other primer pairs, and inverse PCR analysis, revealed an additional truncated T-DNA copy of 1050 nucleotides adjacent to the left border of the complete copy in this line. Sequencing of this truncated T-DNA revealed that it represented an inverted copy of part of the right half of the original construct. This special feature would allow the inverted repeat to pair with right border sequences of the complete copy. This would explain the frequently observed reversion resulting in transgene loss as due to intrachromosomal base-pairing leading to double-stranded loops of single-stranded DNA during mitotic cell divisions.     

Nucleosome unfolding during DNA repair in normal and xeroderma pigmentosum (group C) human cells

The fate of nucleosomes during nucleotide excision repair is unclear. We have used organomercurial chromatography to capture accessible thiol groups of proteins at (or near) nascent repair sites in normal and xeroderma pigmentosum (group C) human cells. The reactive groups include cysteine 110 of histone H3, which is exposed in unfolded nucleosomes. Immediately after UV irradiation and a short pulse labeling of repair patches, intact nuclei were digested with restriction enzymes to release approximately 18% of the chromatin into soluble fragments, which are enriched (approximately 4-fold) in a constitutively transcribed gene. Upon organomercurial affinity fractionation, approximately 1.8% of the soluble chromatin remains bound in high salt (0.5 M NaCl) and is released with dithiothreitol. In normal cell chromatin, this fraction is enriched in nascent repair patches (1.5-1.8-fold) over the unbound fraction. This enrichment decreases following short chase periods with a time course similar to the loss of enhanced nuclease sensitivity of these regions (t 1/2 approximately 30 min). Much less enrichment of nascent repair patches is observed in the thiol-reactive fraction from XPC cells, which repair primarily the transcribed strand of active genes. These results suggest that transient nucleosome unfolding occurs during nucleotide excision repair in normal human cells, and this unfolding may require the XPC protein.     

Decreased accumulation as a mechanism of resistance to cis-diamminedichloroplatinum(II) in cervix carcinoma HeLa cells: relation to DNA repair

In vivo transport in plasma and in vitro transfer of ebselen to binding sites in the hepatocyte were studied. More than 90% of intravenously administered ebselen in mouse plasma is bound by selenium-sulfur bonds to reactive thiols in serum albumin. In in vitro experiments the uptake of [14C]-ebselen from a complex prepared with bovine serum albumin (BSA) was determined in isolated perfused rat liver. Radioactive ebselen metabolites were excreted into bile. In isolated hepatocytes, radioactivity was bound to all subcellular organelles. Ebselen is transferred from the BSA complex to membrane-associated proteins after reductive cleavage of the Se-S bond effected by endogenous protein thiols. In contrast, when proteins were separated by dialysis membranes, ebselen transfer from its BSA complex occurred only in the presence of externally added reductants. Among the physiological reductants tested, ebselen release from the BSA complex was highest with glutathione (75%) and lowest with ascorbic acid (less than 10%). Quantitative release of ebselen from its BSA complex was only achieved by the combined action of reductant, notably 2-mercaptoethanol, and guanidine thiocyanate, suggesting that ebselen interacts with proteins by covalent Se-S bonds as well as by ionic charge interactions.     

"Differential effects of posterior septal lesions on dispositional and representational memory": Correction to Thomas and Gash (1986).

Reports an error in "Differential effects of posterior septal lesions on dispositional and representational memory" by Garth J. Thomas and Don M. Gash (Behavioral Neuroscience, 1986[Oct], Vol 100[5], 712-719). A phrase was erroneously deleted from the text. In the seventh paragraph on p. 713, the second sentence should read as follows: Early in training individual differences were great, but by the end of adaptation training, individual differences were quite small and all rats responded at close to asymptotic speeds. (The following abstract of the original article appeared in record 1987-06585-001.) A distinction between 2 classes of memory has been made in terms of the sensory availability of cues at the time of making discriminations that are influenced by past experience. Three tasks objectively defining this distinction were learned in a T-maze by 36 male Long-Evans rats in 3 groups: (a) a delayed non-matching-to-sample (DNMTS) that depended on representational memory; (b) a simple sensory discrimination (SD) that depended on dispositional memory; and (c) a more difficult discrimination that also depended on dispositional memory, called the simultaneous conditional discrimination (SCD). The DNMTS and SD tasks were acquired quickly; the SCD task took many more trials. Posterior septal lesions impaired DNMTS performance but had no effect on retention of tasks that depended on dispositional memory. Results indicate that dispositional and representational memory systems have at least partially distinct anatomical substrates in the brain and that it is the representational and not the conditional aspects of the DNMTS task that are impaired by the septal lesions. (21 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Medial preoptic lesions disrupt parental behavior in both male and female California mice (Peromyscus californicus).

California mice (Peromyscus californicus) are monogamous and naturally biparental, making them an ideal species in which to study the neural basis of paternal behavior. A male or female from each male-female pair was given an electrolytic or sham lesion in the medial preoptic area (MPOA), an area known to be critical for the expression of maternal behavior in rats, and retested for parental responsiveness. MPOA-lesioned males and females showed significantly longer latencies to show parental behavior and spent significantly less time near pups, sniffing pups, and licking pups than sham-lesioned mice. However, MPOA lesions did not reduce time spent hovering over pups. The results suggest that the neural mechanisms mediating paternal behavior are similar to those mediating maternal behavior in this species. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The overlearning-extinction effect and successive negative contrast in honeybees (Apis mellifera).

In 3 experiments with 169 free-flying honeybees, the overlearning-extinction effect previously demonstrated by the present authors (see record 1982-09095-001) was replicated under different conditions and shown to depend on magnitude of reinforcement. The effect appeared in training with a 50% sucrose solution but not with a 20% solution. Results prompted a 4th experiment, with 25 Ss, in which successive negative contrast was demonstrated. Ss were disturbed to find the 20% solution on a distinctive target that always before had been baited with the 50% solution. It is concluded that the overlearning-extinction effect is an instance of contrast and can be understood in terms of frustration engendered by unrealized anticipation of reinforcement. (28 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)