Endometrial polyp harboring a primary B-cell non-Hodgkin lymphoma: a useful in-office hysteroscopic approach.

A non-menopausal women underwent gynecological evaluation for spotting and menstrual irregularities. After first line gynecological assessments, the patient underwent office hysteroscopy. By using an in-office technique, two isthmic endometrial polyps and one cervical polyp were removed. One endometFial polyp was found to harbor a B-cell high-grade lymphoma just on the apex (found to be necrotic). The following staging examinatioIns and the pathological assessment of the endometrium, the uterus, the adnexa, and the lymphatic regional nodes did not find any localization of the lymphoma. No additional treatments were done. The patient is alive and disease-free at 18 months follow-up.

In vivo repair of DNA damage induced by X-rays in the early stages of mouse fertilization, and the influence of maternal PARP1 ablation.

The early pronucleus stage of the mouse zygote has been characterised in vitro as radiosensitive, due to a high rate of induction of chromosome-type chromosome abnormalities (CA). We have investigated the repair of irradiation induced double strand DNA breaks in vivo by γH2AX foci and first cleavage metaphase analysis. Breaks were induced in sperm and in the early zygote stages comprising sperm chromatin remodelling and early pronucleus expansion. Moreover, the role of PARP1 in the formation and repair of spontaneous and radiation-induced double strand breaks in the zygote was evaluated by comparing observations in C57BL/6J and PARP1 genetically ablated females. The results confirmed in vivo that the rate of chromosome aberration induction by X-rays was approximately 3-fold higher in the zygote than in mouse lymphocytes. This finding was related to a diminished efficiency of double strand break signalling, as shown by a lower rate of γH2AX radiation-induced foci compared to that measured in most other somatic cell types. The spontaneous frequency of CA in PARP1 depleted zygotes was slightly but significantly higher than in wild type zygotes. Also, these zygotes showed some impairment of the radiation-induced DNA Damage Response when exposed closer to the start of S-phase, revealed by a higher number of γH2AX foci and a longer cell cycle delay. The rate of chromosome aberrations, however, was not elevated over that of wild type zygotes, possibly thanks to backup repair pathways and/or selection mechanisms against damaged cells. When comparing with the literature data on irradiation induced CA in mouse zygotes in vitro, the levels of induction were strikingly similar as was the frequency of misrepair of double strand breaks (γH2AX foci). This result can be reassuring for in vitro human gamete and embryo handling, because it shows that culture conditions do not significantly affect double strand DNA break repair.

(-)-Stepholidine blocks expression, but not development, of cocaine conditioned place preference in rats.

The purpose of this study was to investigate the effects of (-)-stepholidine (SPD), a compound with dopamine D1 partial agonist and D2/D3 antagonist properties, on the development and expression of cocaine conditioned place preference (CPP). Subjects (N = 65; male Long Evans rats) were tested using a CPP procedure consisting of 3 phases: (1) a 15-min pre-exposure session where animals could explore each compartment freely, (2) eight 30-min conditioning sessions where animals were restricted to one side or the other with cocaine (10 mg/kg) or saline, respectively, on alternating days and (3) a 15-minute preference test session where animals could explore each compartment freely. To test the effects of SPD on expression of cocaine CPP, rats were administered vehicle (distilled water with 20 % DMSO), 10, 15 or 20 mg/kg SPD (intraperitoneally) 30 min prior to the test session. We found that 20 mg/kg of SPD significantly blocked the expression of cocaine CPP. To test the effects of SPD on the development of CPP, 0 (vehicle), 10, 15 or 20mg/kg SPD were administered 30 min prior to each cocaine conditioning session and vehicle before each saline conditioning session; no treatment was given prior to the test session. A preference test showed that each SPD group maintained a CPP similar to the vehicle group. These data indicate that SPD can block the expression of a cocaine CPP but has no effect on its development, suggesting that it inhibits the effects of cocaine cues on cocaine incentive motivated behavior. These results suggest that SPD may be a potential treatment for cue-driven aspects of cocaine use disorder.

KIT and PDGFRalpha mutations in 104 patients with gastrointestinal stromal tumors (GISTs): a population-based study.

BACKGROUND: The prognostic significance of KIT or platelet-derived growth factor receptor alpha (PDGFRalpha) mutations in gastrointestinal stromal tumors (GISTs) is still controversial. PATIENTS AND METHODS: In all, 104 patients were diagnosed with GISTs by KIT immunoreactivity; tumor DNA was sequenced for the presence of mutations in KIT exons 9, 11, 13 and 17 and in PDGFRalpha exons 12 and 18. Disease-free survival (DFS) was analyzed in 85 radically resected patients. RESULTS: KIT mutations occurred in exon 11 (69), in exon 9 (11) and in exon 17 (1). PDGFRalpha mutations were detected in exon 18 (10) and in exon 12 (3). Ten GISTs were wild type. Exon 11 mutations were as follows: deletions in 42 cases and point mutations in 20 cases and insertions and duplications, respectively, in 2 and 5 cases. A better trend in DFS was evident for duplicated and point-mutated exon 11 KIT GISTs. There was a significant association between PDGFRalpha mutations, gastric location and lower mitotic index. Moreover, PDGFRalpha-mutated GISTs seemed to have a better outcome. CONCLUSIONS: Point mutations and duplications in KIT exon 11 are associated with a better clinical trend in DFS. PDGFRalpha-mutated GISTs are preferentially localized in the stomach and seem to have a favorable clinical behavior.

Evaluation of aneugenic effects of bisphenol A in somatic and germ cells of the mouse.

Bisphenol A (BPA) is a synthetic monomer widely used to polymerize polycarbonate plastics and resins. It is shown in vitro to interfere with microtubules, producing aberations in mitotic and meiotic spindles. An increase of meiotic abnormalities in untreated female mice from an experimental colony was temporally correlated with the accidental release of BPA from polycarbonate cages and bottles damaged by inadvertent treatment with harsh alkaline detergents [P.A. Hunt, K.E. Koehler, M. Susiarjo, C.A. Hodges, A. Ilagan, R.C. Voigt, S. Thomas, B.F. Thomas, T.J. Hassold, Bisphenol A exposure causes meiotic aneuploidy in the female mouse, Curr. Biol. 13 (2003) 546-553]. In the present study, potential aneugenic effects of BPA on mouse male and female germ cells and bone marrow cells have been evaluated after acute, sub-chronic or chronic in vivo exposure. Female mice were orally treated with a single BPA dose, with 7 daily administrations or exposed for 7 weeks to BPA in drinking water. No significant induction of hyperploidy or polyploidy was observed in oocytes and zygotes at any treatment condition. The only detectable effect was a significant increase of metaphase II oocytes with prematurely separated chromatids after chronic exposure; this effect, however, had no irreversible consequence upon the fidelity of chromosome segregation during the second meiotic division, as demonstrated by the normal chromosome constitution of zygotes under the same exposure condition. With male mice, no delay of meiotic divisions was found after six daily oral doses of BPA with the BrdU assay. Similarly, no induction of hyperploidy and polyploidy was shown in epydidimal sperm hybrized with probes for chromosomes 8, X and Y, 22 days after six daily oral BPA doses. Finally, two daily oral BPA doses did not induce any increase of micronucleus frequencies in polychromatic erythrocytes of mouse bone marrow. In conclusion, our results do not add evidence to the suspected aneugenic activity of BPA and suggest that other factors or co-factors should be considered to explain the unexpected burst of meiotic abnormalities previously attributed to accidental BPA exposure.

The strength of reward-related learning depends on the degree of activation of ventral tegmental area dopamine neurons.

We tested whether (1) the capacity of a reward-associated conditioned stimulus (CS) to cause conditioned activation of ventral tegmental area (VTA) dopamine (DA) neurons is associated with its capacity to elicit conditioned approach responses and (2) whether the acquisition of these capacities by a CS requires N-methyl-D-aspartate (NMDA) and muscarinic acetylcholine (mACh) receptor stimulation. Rats were trained to emit a conditioned approach response to a light CS that was previously paired with food and were treated systemically with scopolamine (a mACh receptor antagonist) or MK-801 (an NMDA receptor antagonist) either prior to each conditioning session (during which animals experienced paired CS and food presentations) or prior to the conditioned approach (CS-only) test. Brains were harvested after the CS-only test and processed for tyrosine hydroxylase (TH) (DA cells) and c-fos in the VTA. When animals received scopolamine or MK-801 treatment prior to conditioning sessions we observed significantly fewer TH-labeled (i.e., DA) cells in the VTA that expressed c-fos and significantly less conditioned approach responding during the CS-only test. Further analysis showed a correlation between the number of VTA DA cells activated and the number of conditioned approach responses. Treatments made prior to the CS-only test did not affect responding. Altogether these results suggest that the degree to which a CS elicits conditioned approach depends partially on the degree to which the CS activates VTA DA cells and that the acquisition of both of these capacities by a CS requires mACh and NMDA receptor stimulation.

(-)-Stepholidine reduces cue-induced reinstatement of cocaine seeking and cocaine self-administration in rats.

BACKGROUND: Dopamine receptors are implicated in cocaine reward and seeking. We hypothesize that (-)-stepholidine, a dopamine D1/D2/D3 multi-receptor agent, would be effective in reducing cocaine reward and seeking in an animal model. We investigated the effects of (-)-stepholidine in cue-induced reinstatement of cocaine seeking and cocaine self-administration (reward). METHODS: Cue-induced reinstatement experiment: Rats were trained to press a lever reinforced by cocaine (1 mg/kg/injection) for 15 consecutive daily sessions, after which the response was extinguished by withholding cocaine and cocaine-paired cues (light and pump activation). This was followed by a cue-induced reinstatement test where subjects were exposed to two cocaine cue presentations and presses on the active lever produced cues. Subjects were treated with one of four (-)-stepholidine doses prior to the reinstatement test. Cocaine self-administration (reward) experiment: Rats were trained to self-administer cocaine under a progressive ratio schedule of reinforcement. After stable breakpoints were established, rats were injected with four doses of (-)-stepholidine prior to testing; each dose was injected prior to a separate test session with no-treatment sessions intervening to re-establish break points. RESULTS: (-)-Stepholidine significantly reduced cue-induced reinstatement of cocaine seeking in a dose-related manner. Additionally, (-)-stepholidine significantly reduced break points for cocaine reward. (-)-Stepholidine did not significantly affect locomotor activity. CONCLUSIONS: (-)-Stepholidine reduces cue-induced reinstatement of cocaine seeking and cocaine reward, suggesting that it may be useful in treating relapse in cocaine addiction.

Effect of p53 haploinsufficiency on melphalan-induced genotoxic effects in mouse bone marrow and peripheral blood.

Mice heterozygous for a p53 null mutation develop tumours induced by genotoxic carcinogens with a shorter latency than wild type mice and have been proposed as an alternate animal model for carcinogenicity testing. Some literature data suggest that p53+/- mice might also be more sensitive to the short-term effects of genotoxic agents and manifest a haploinsufficiency phenotype that could contribute to the higher tumour susceptibility. We have compared the induction of micronuclei in bone marrow and blood of p53+/- and p53+/+ isogenic mice after treatment with a single or multiple doses of melphalan (MLP), a crosslinking genotoxic carcinogen. We have also characterized the mechanism of micronucleus induction with CREST staining of kinetochore proteins to distinguish between chromosome break- and chromosome loss-induced micronuclei. Significant increases of micronucleated bone marrow polychromatic erythrocytes and blood reticulocytes were induced under all MLP exposure conditions. The frequency of micronucleated blood erythrocytes increased linearly with duration of exposure. Micronuclei were essentially a consequence of chromosome break events. After a single MLP dose, a significant reduction of the frequency of polychromatic erythrocytes in bone marrow of p53+/+ animals suggested the induction of cytotoxicity/cell cycle delay. This effect was not observed in p53+/- mice. We believe this finding to provide some evidence of a haploinsufficiency phenotype in the modulation of cell cycle/apoptotic pathways mediated by the p53 protein. In bone marrow of wild type mice, an increased effect of multiple MLP doses was detected over that of a single administration, whereas, in p53+/- mice, no differential effect was found of different exposure durations. Possibly, the probability of micronucleus formation increased under chronic exposure because of increased cell division in response to peripheral anemia and a reduction of p53 protein level had a small effect on cell cycle modulation and on such indirect mechanism of micronucleus induction. However, pairwise comparisons between the frequencies of cells with micronuclei in wild type and p53+/- mice under all exposure conditions did not show statistically significant differences, suggesting that the observed effects of p53 haploinsufficiency were weak and temporary and a higher/faster induction of irreversible chromosome damage could not account for the increased susceptibility of p53+/- mice to MLP-induced tumours.

Blockade of muscarinic acetylcholine receptors in the ventral tegmental area blocks the acquisition of reward-related learning.

In the present study we investigated whether stimulation of muscarinic acetylcholine (mACh) receptors in the ventral tegmental area (VTA) plays a role in the acquisition of food-based conditioned approach learning. Rats were exposed to 3 (in Experiment 1) or 7 (in Experiment 2) conditioning sessions in which 30, randomly presented light (CS) presentations were paired with delivery of food pellets (US), followed by one session with no light or food and finally one CS-only test session with only light stimulus presentations. Bilateral microinjections of scopolamine (a mACh receptor antagonist) were made either prior to each conditioning session (Experiment 1; to test effects on acquisition) or prior to the CS-only test (Experiment 2; to test effects on performance of the learned response). Scopolamine produced a dose-related significant reduction in the acquisition of conditioned approach but had no effect on its performance. These results suggest that mACh receptor stimulation in the VTA plays a necessary role in the acquisition of reward-related learning.

No evidence that environmental enrichment during rearing protects against cocaine behavioral effects but as an intervention reduces an already established cocaine conditioned place preference.

OBJECTIVES: Environmental enrichment (EE) produces differential effects on psychostimulant-related behaviors. Therefore, we investigated whether the timing of EE exposure - during rearing and before cocaine exposure versus in adulthood and after cocaine exposure might be a determining factor. METHODS: In Experiment 1, rats reared with EE or not (non-EE) were conditioned with cocaine (5, 10 or 20mg/kg) in one compartment of a CPP apparatus and saline in the other, and later tested for cocaine CPP. In Experiment 2, locomotor activity in response to repeated injections of saline or cocaine was measured in rats raised with EE or non-EE. In Experiment 3 we measured the effects of EE or non-EE during rearing on food-based conditioned approach learning. In Experiment 4, rats were exposed to cocaine CPP conditioning then underwent 60days of EE or non-EE treatment after which they were tested for cocaine CPP. RESULTS: Our results show that rearing in EE did not reduce cocaine CPP or cocaine-induced locomotor activity (Experiments 1 and 2) but significantly facilitated conditioned approach learning (Experiment 3). On the other hand, EE treatment introduced after cocaine conditioning significantly reduced the expression of cocaine CPP (Experiment 4). CONCLUSIONS: These findings suggest that EE does not protect against cocaine's rewarding and stimulant effects but can reduce already established cocaine effects, suggesting that EE might be an effective treatment for cocaine addiction-related behaviors.

Bone marrow histopathological and molecular changes of small B-cell lymphomas after rituximab therapy: comparison with clinical response and patients outcome.

This study correlates bone marrow changes after Rituximab (RTX) treatment with the clinical characteristics and outcome of 26 patients with small B-cell lymphomas. The percentage, phenotypic profile and clonality pattern of bone marrow lymphoid infiltrate were analysed before and after RTX treatment. Clinical, histological and molecular responses to RTX were correlated to the clinical outcome of the patients. Sixteen out of twenty-six patients obtained a complete clinical remission (CR). A favourable histology--follicular lymphoma (FL), hairy cell leukaemia (HCL) and marginal zone lymphoma (MZL)--was associated with a higher frequency of clinical CR and histological remission (HR), in comparison with mantle cell lymphoma (MCL), chronic lymphocytic leukaemia (CLL) and lymphoplasmacytic lymphoma (LPL). Two patterns of bone marrow HR were observed: 1) complete lymphoid cell disappearance (9 patients); or 2) nodular/interstitial T-cell infiltration (10 patients). Three histological persistence (HP) patterns were observed: 1) persistence of CD20+ small lymphoid cells in 1 patient with MCL; 2) loss of CD20 antigen expression in 4 patients with CLL; or 3) persistence only of clusters of monotypic plasma cells in 2 patients with LPL. CR and HR were strongly correlated. The percentage of lymphomatous infiltrate after RTX was higher in patients who subsequently died of the disease. Molecular response showed no correlations with the further clinical course in 12 patients achieving a complete clinical remission. In conclusion, bone marrow morphological and immunohistochemical analysis with a restricted panel of antibodies is useful to avoid 42% false positive and 85% false negative interpretations. Persistence of monoclonality after RTX might have a role in evaluating the molecular pattern of CD20-negative clones that can emerge after RTX as a tumoral escape to therapy.

Treatment with a muscarinic acetylcholine receptor antagonist impairs the acquisition of conditioned reward learning in rats.

The neural mechanisms whereby a reward-associated stimulus gains reinforcing properties and comes to function as a conditioned reward (CR) are not understood. We propose that muscarinic acetylcholine (mACh) receptor stimulation is necessary for this type of learning. Here we tested the hypothesis that mACh receptor antagonism, with scopolamine, would attenuate the acquisition by a food-related stimulus of the capacity to function as a CR. Rats were exposed to 5 pre-exposure sessions during which two levers were present, one producing a light and the other a tone when pressed. This was followed by 3 conditioning sessions in which the levers were absent and the rats were presented with 30 light-food pairings delivered randomly. In the test session, the levers were present and presses on both levers were recorded. Different groups of rats received intraperitoneal injections of scopolamine (0, 0.375, 0.75 and 1mg/kg) either prior to each conditioning session or prior to the test session. All groups showed significantly greater responding on the light lever in the test compared to the pre-exposure sessions, demonstrating the CR effect. In animals treated prior to conditioning the scopolamine groups pressed significantly less on the light lever than the vehicle group. In animals treated prior to the test the increased lever pressing for light was similar for all groups. These data suggest that scopolamine impaired the acquisition of CR but not its expression. The results support the hypothesis that mACh receptor stimulation is important for the acquisition by reward-associated stimuli of the ability to function as CRs.

Environmental enrichment as a potential intervention for heroin seeking.

BACKGROUND: Heroin-related cues can trigger craving and relapse in addicts or heroin seeking in rats. In the present study we investigated whether environmental enrichment (EE) implemented after heroin exposure can reduce cue-induced reinstatement of heroin seeking and expression of heroin conditioned place preference. METHODS: In Experiment 1, male Long Evans rats that already acquired a heroin self-administration habit, were housed in enriched or non-enriched environments, underwent extinction training and later were tested for cue-induced reinstatement of heroin seeking. In Experiment 2, rats were conditioned with heroin in one compartment of a CPP apparatus and saline in the other, exposed to 30days of enrichment or no enrichment and were later tested for heroin CPP. RESULTS: The results showed that exposure to EE significantly reduced responding during the reinstatement test (Experiment 1) and prevented the expression of heroin CPP (Experiment 2). CONCLUSION: Our findings suggest that EE can be an effective behavioral approach to diminish the effects of conditioned cues on heroin seeking.

Dopamine D1 and D3 receptor interactions in cocaine reward and seeking in rats.

RATIONALE: Animal research has demonstrated a role of dopamine D1 and D3 receptors in cocaine reward and seeking. PURPOSE AND METHODS: Here, we investigated the potential interaction of these two dopamine receptors in cue-induced reinstatement of cocaine seeking, cocaine conditioned place preference (CPP), and cocaine self-administration in rats. RESULTS: The co-administration of a D3 receptor antagonist, NGB 2904 and a D1 partial agonist, SKF 77434, of doses which when administered individually produced no significant effects, prior to reinstatement or CPP tests significantly reduced lever pressing and time spent in the cocaine-paired environment, suggesting synergistic effects of the combined compounds on cocaine seeking. When given to rats self-administering cocaine under a progressive ratio schedule of reinforcement doses of NGB 2904 which were ineffective alone significantly enhanced the break point-reducing effects of SKF 77434. CONCLUSIONS: Our results indicate that the combined treatment with a D1 receptor partial agonist and D3 receptor antagonist produces robust decreases in cocaine seeking and reward. This suggests an interaction between dopamine D1 and D3 receptors in cocaine-related behaviors.

The dopamine D3 receptor antagonist, SR 21502, facilitates extinction of cocaine conditioned place preference.

BACKGROUND: Pharmacotherapeutic agents that could facilitate extinction of cocaine cues would be useful in the treatment of cocaine addiction. We tested whether SR 21502, a selective dopamine (DA) D3 receptor antagonist, can facilitate extinction of cocaine conditioned place preference (CPP) in rats. METHODS: In experiment 1, cocaine (10mg/kg) CPP was first established and then extinguished. During the extinction phase the rats were injected with SR 21502 and placed in the previously cocaine-paired compartment for four sessions and vehicle in the other compartment on four alternating sessions. The rats were then tested again for cocaine CPP. In experiment 2, different groups of rats were trained to associate SR 21502 with one compartment and saline with the other. RESULTS: In experiment 1, the animals spent significantly more time in the cocaine-paired compartment after cocaine conditioning than they did before conditioning. Subsequently, the animals treated with SR 21502 during the extinction phase spent significantly less time in the cocaine-paired compartment than the vehicle group. In experiment 2, animals conditioned with SR 21502 preferred neither side of the CPP apparatus, indicating that SR 21502 produced no effects of its own. CONCLUSIONS: These findings suggest that treatment with SR 21502, a DA D3 receptor antagonist, in the presence of cocaine cues can facilitate extinction of cocaine CPP and further suggest that this compound might be an effective cocaine addiction treatment.

Blockade of D1 dopamine receptors in the ventral tegmental area decreases cocaine reward: possible role for dendritically released dopamine.

This study was designed to assess the involvement of D1 dopamine actions in the ventral tegmental area (VTA) on intravenous cocaine self-administration. Rats were trained to self-administer intravenous injections of cocaine (1.0 mg/kg per injection) on a fixed-ratio 1 (FR-1) schedule or a progressive ratio (PR) schedule of reinforcement and then were tested under the influence of bilateral VTA injections of the D1 dopamine receptor antagonist SCH 23390 or the 5-HT2 receptor antagonist ketanserin. SCH 23390 increased cocaine self-administration on the FR-1 schedule but decreased it on the PR schedule. Injections of ketanserin were ineffective, as were injections of SCH 23390 in a site 1 mm dorsal or 1 mm rostral to the effective VTA site. These data suggest a role for dendritically released dopamine, presumably acting through D1 receptors located on the axons of GABAergic or glutamatergic inputs to the VTA, in the effectiveness of cocaine reward.

Dopamine fluctuations in the nucleus accumbens during maintenance, extinction, and reinstatement of intravenous D-amphetamine self-administration.

Moment-to-moment fluctuations of nucleus accumbens dopamine (DA) were determined in rats self-administering or passively receiving "yoked" intravenous infusions of D-amphetamine. The initial lever presses of each session caused elevations in DA concentration, usually to an initial peak that was not maintained throughout the rest of the session. As the initial ("loading") injections were metabolized, DA levels dropped toward baseline but were sustained at elevated plateaus by subsequent lever pressing that was spaced throughout the remainder of the 3 hr sessions. During this period, DA levels fluctuated phasically, time-locked to the cycle of periodic lever pressing. Consistent with the known pharmacological actions and dynamics of amphetamine, peak DA elevations were seen approximately 10-15 min after each injection, and the mean DA level was at a low point in the phasic cycle at the time of each new lever press. During extinction periods when saline was substituted for amphetamine, DA levels dropped steadily toward baseline levels despite a dramatic increase in (now-unrewarded) lever pressing. Noncontingent injections during extinction reinstated lever-pressing behavior and increased nucleus accumbens DA concentrations. These data are consistent with the hypothesis that under the conditions of this experiment-during periods of amphetamine intoxication in well-trained animals-the timing of amphetamine self-administration comes primarily under the control of extracellular DA concentrations. The probability of lever pressing during the maintenance phase is highest when DA concentrations fall near a characteristic trigger point, a trigger point that is significantly elevated above baseline, and falls as DA concentrations fall below or increase above that trigger point.

A multi-biomarker analysis of DNA damage in automobile painters.

The genotoxic effects associated with automobile painting were analyzed using a panel of biomarkers. Chromosomal aberrations (CAs), sister chromatid exchange (SCE), and micronuclei were evaluated in 25 car painters (12 smokers, 13 nonsmokers) working in different automobile paint-shops in Italy and in 37 control subjects. The controls were healthy blood donors (14 smokers, 23 non-smokers) that were matched with the experimental population for gender and age. Air samples were analyzed regularly at the work places, and elevated concentrations of benzene and toluene were detected consistently. The exposed group had higher frequencies of CAs (both chromosome- and chromatid-type), micronuclei, and SCE (P < 0.5 - P < 0.001). Furthermore, exposed and control subjects were also genotyped for GSTM1 and GSTT1 polymorphism. No significant associations were detected between the biomarker responses and either the GSTM1 or GSTT1 genotype of the subjects, but the small sample size does not allow definite conclusions on the relationship between the genetic polymorphism and the biomarkers. The results indicate that automobile painters have increased levels of clastogenic and possible aneugenic damage and that smoking may be a confounding factor for the responses.

c-Fos induction in mesotelencephalic dopamine pathway projection targets and dorsal striatum following oral intake of sugars and fats in rats.

Overconsumption of nutrients high in fats and sugars can lead to obesity. Previous studies indicate that sugar or fat consumption activate individual brain sites using Fos-like immunoreactivity (FLI). Sugars and fats also elicit conditioned flavor preferences (CFP) that are differentially mediated by flavor-flavor (orosensory: f/f) and flavor-nutrient (post-ingestive: f/n) processes. Dopamine (DA) signaling in the medial prefrontal cortex (mPFC), the amygdala (AMY) and the nucleus accumbens (NAc), has been implicated in acquisition and expression of fat- and sugar-CFP. The present study examined the effects of acute consumption of fat (corn oil: f/f and f/n), glucose (f/f and f/n), fructose, (f/f only), saccharin, xanthan gum or water upon simultaneous FLI activation of DA mesotelencephalic nuclei (ventral tegmental area (VTA)) and projections (infralimbic and prelimbic mPFC, basolateral and central-cortico-medial AMY, core and shell of NAc as well as the dorsal striatum). Consumption of corn oil solutions, isocaloric to glucose and fructose, significantly increased FLI in all sites except for the NAc shell. Glucose intake significantly increased FLI in both AMY areas, dorsal striatum and NAc core, but not in either mPFC area, VTA or Nac shell. Correspondingly, fructose intake significantly increased FLI in the both AMY areas, the infralimbic mPFC and dorsal striatum, but not the prelimbic mPFC, VTA or either NAc area. Saccharin and xanthan gum intake failed to activate FLI relative to water. When significant FLI activation occurred, highly positive relationships were observed among sites, supporting the idea of activation of a distributed brain network mediating sugar and fat intake.