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1.
J Geophys Res Planets ; 128(1): e2022JE007185, 2023 Jan.
Article in English | MEDLINE | ID: mdl-37034460

ABSTRACT

The Mars Science Laboratory rover, Curiosity, explored the clay mineral-bearing Glen Torridon region for 1 Martian year between January 2019 and January 2021, including a short campaign onto the Greenheugh pediment. The Glen Torridon campaign sought to characterize the geology of the area, seek evidence of habitable environments, and document the onset of a potentially global climatic transition during the Hesperian era. Curiosity roved 5 km in total throughout Glen Torridon, from the Vera Rubin ridge to the northern margin of the Greenheugh pediment. Curiosity acquired samples from 11 drill holes during this campaign and conducted the first Martian thermochemolytic-based organics detection experiment with the Sample Analysis at Mars instrument suite. The lowest elevations within Glen Torridon represent a continuation of lacustrine Murray formation deposits, but overlying widespread cross bedded sandstones indicate an interval of more energetic fluvial environments and prompted the definition of a new stratigraphic formation in the Mount Sharp group called the Carolyn Shoemaker formation. Glen Torridon hosts abundant phyllosilicates yet remains compositionally and mineralogically comparable to the rest of the Mount Sharp group. Glen Torridon samples have a great diversity and abundance of sulfur-bearing organic molecules, which are consistent with the presence of ancient refractory organic matter. The Glen Torridon region experienced heterogeneous diagenesis, with the most striking alteration occurring just below the Siccar Point unconformity at the Greenheugh pediment. Results from the pediment campaign show that the capping sandstone formed within the Stimson Hesperian aeolian sand sea that experienced seasonal variations in wind direction.

2.
J Geophys Res Planets ; 127(6): e2021JE007096, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35865672

ABSTRACT

Gale crater, the field site for NASA's Mars Science Laboratory Curiosity rover, contains a diverse and extensive record of aeolian deposition and erosion. This study focuses on a series of regularly spaced, curvilinear, and sometimes branching bedrock ridges that occur within the Glen Torridon region on the lower northwest flank of Aeolis Mons, the central mound within Gale crater. During Curiosity's exploration of Glen Torridon between sols ∼2300-3080, the rover drove through this field of ridges, providing the opportunity for in situ observation of these features. This study uses orbiter and rover data to characterize ridge morphology, spatial distribution, compositional and material properties, and association with other aeolian features in the area. Based on these observations, we find that the Glen Torridon ridges are consistent with an origin as wind-eroded bedrock ridges, carved during the exhumation of Mount Sharp. Erosional features like the Glen Torridon ridges observed elsewhere on Mars, termed periodic bedrock ridges (PBRs), have been interpreted to form transverse to the dominant wind direction. The size and morphology of the Glen Torridon PBRs are consistent with transverse formative winds, but the orientation of nearby aeolian bedforms and bedrock erosional features raise the possibility of PBR formation by a net northeasterly wind regime. Although several formation models for the Glen Torridon PBRs are still under consideration, and questions persist about the nature of PBR-forming paleowinds, the presence of PBRs at this site provides important constraints on the depositional and erosional history of Gale crater.

3.
J Geophys Res Planets ; 125(11): e2019JE006322, 2020 Nov.
Article in English | MEDLINE | ID: mdl-33282614

ABSTRACT

Images from the Mars Science Laboratory (MSL) mission of lacustrine sedimentary rocks of Vera Rubin ridge on "Mt. Sharp" in Gale crater, Mars, have shown stark color variations from red to purple to gray. These color differences crosscut stratigraphy and are likely due to diagenetic alteration of the sediments after deposition. However, the chemistry and timing of these fluid interactions is unclear. Determining how diagenetic processes may have modified chemical and mineralogical signatures of ancient Martian environments is critical for understanding the past habitability of Mars and achieving the goals of the MSL mission. Here we use visible/near-infrared spectra from Mastcam and ChemCam to determine the mineralogical origins of color variations in the ridge. Color variations are consistent with changes in spectral properties related to the crystallinity, grain size, and texture of hematite. Coarse-grained gray hematite spectrally dominates in the gray patches and is present in the purple areas, while nanophase and fine-grained red crystalline hematite are present and spectrally dominate in the red and purple areas. We hypothesize that these differences were caused by grain-size coarsening of hematite by diagenetic fluids, as observed in terrestrial analogs. In this model, early primary reddening by oxidizing fluids near the surface was followed during or after burial by bleaching to form the gray patches, possibly with limited secondary reddening after exhumation. Diagenetic alteration may have diminished the preservation of biosignatures and changed the composition of the sediments, making it more difficult to interpret how conditions evolved in the paleolake over time.

4.
Geosphere (Boulder) ; 16(6): 1508-1537, 2020 Dec 01.
Article in English | MEDLINE | ID: mdl-33304202

ABSTRACT

Extraformational sediment recycling (old sedimentary rock to new sedimentary rock) is a fundamental aspect of Earth's geological record; tectonism exposes sedimentary rock, whereupon it is weathered and eroded to form new sediment that later becomes lithified. On Mars, tectonism has been minor, but two decades of orbiter instrument-based studies show that some sedimentary rocks previously buried to depths of kilometers have been exposed, by erosion, at the surface. Four locations in Gale crater, explored using the National Aeronautics and Space Administration's Curiosity rover, exhibit sedimentary lithoclasts in sedimentary rock: At Marias Pass, they are mudstone fragments in sandstone derived from strata below an erosional unconformity; at Bimbe, they are pebble-sized sandstone and, possibly, laminated, intraclast-bearing, chemical (calcium sulfate) sediment fragments in conglomerates; at Cooperstown, they are pebble-sized fragments of sandstone within coarse sandstone; at Dingo Gap, they are cobble-sized, stratified sandstone fragments in conglomerate derived from an immediately underlying sandstone. Mars orbiter images show lithified sediment fans at the termini of canyons that incise sedimentary rock in Gale crater; these, too, consist of recycled, extraformational sediment. The recycled sediments in Gale crater are compositionally immature, indicating the dominance of physical weathering processes during the second known cycle. The observations at Marias Pass indicate that sediment eroded and removed from craters such as Gale crater during the Martian Hesperian Period could have been recycled to form new rock elsewhere. Our results permit prediction that lithified deltaic sediments at the Perseverance (landing in 2021) and Rosalind Franklin (landing in 2023) rover field sites could contain extraformational recycled sediment.

5.
J Psychopathol Behav Assess ; 40(3): 367-375, 2018 Sep 01.
Article in English | MEDLINE | ID: mdl-30270970

ABSTRACT

To compare community diagnoses of Autism Spectrum Disorder (ASD) reported by parents to consensus diagnoses made using standardized tools plus clinical observation. 87 participants (85% male, average age 7.4 years), with reported community diagnosis of ASD were evaluated using the Autism Diagnostic Observation Schedule) (ADOS-2), Differential Ability Scale (DAS-II), and Vineland Adaptive Behavior Scales (VABS-II). Detailed developmental and medical history was obtained from all participants. Diagnosis was based on clinical consensus of at least two expert clinicians, using test results, clinical observations, and parent report. 23% of participants with a reported community diagnosis of ASD were classified as non-spectrum based on our consensus diagnosis. ASD and non-spectrum participants did not differ on age at evaluation and age of first community diagnosis. Non-verbal IQ scores and Adaptive Behavior Composite scores were significantly higher in the non-spectrum group compared to the ASD group (104.5 ± 21.7 vs. 80.1 ± 21.6, p < .01; 71.1 ± 15 versus 79.5 ± 17.6, p < .05, respectively). Participants enrolled with community diagnosis of PDD-NOS were significantly more likely to be classified as non-spectrum on the study consensus diagnosis than Participants with Autism or Asperger (36% versus 9.5%, Odds Ratio = 5.4, p < .05). This study shows suboptimal agreement between community diagnoses of ASD and consensus diagnosis using standardized instruments. These findings are based on limited data, and should be further studied, taking into consideration the influence of DSM 5 diagnostic criteria on ASD prevalence.

6.
Appl Environ Microbiol ; 82(8): 2270-2279, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26826234

ABSTRACT

Nitrosomonas europaea is an aerobic nitrifying bacterium that oxidizes ammonia (NH3) to nitrite (NO2 (-)) through the sequential activities of ammonia monooxygenase (AMO) and hydroxylamine dehydrogenase (HAO). Many alkynes are mechanism-based inactivators of AMO, and here we describe an activity-based protein profiling method for this enzyme using 1,7-octadiyne (17OD) as a probe. Inactivation of NH4 (+)-dependent O2 uptake by N. europaea by 17OD was time- and concentration-dependent. The effects of 17OD were specific for ammonia-oxidizing activity, andde novoprotein synthesis was required to reestablish this activity after cells were exposed to 17OD. Cells were reacted with Alexa Fluor 647 azide using a copper-catalyzed azide-alkyne cycloaddition (CuAAC) (click) reaction, solubilized, and analyzed by SDS-PAGE and infrared (IR) scanning. A fluorescent 28-kDa polypeptide was observed for cells previously exposed to 17OD but not for cells treated with either allylthiourea or acetylene prior to exposure to 17OD or for cells not previously exposed to 17OD. The fluorescent polypeptide was membrane associated and aggregated when heated with ß-mercaptoethanol and SDS. The fluorescent polypeptide was also detected in cells pretreated with other diynes, but not in cells pretreated with structural homologs containing a single ethynyl functional group. The membrane fraction from 17OD-treated cells was conjugated with biotin-azide and solubilized in SDS. Streptavidin affinity-purified polypeptides were on-bead trypsin-digested, and amino acid sequences of the peptide fragments were determined by liquid chromatography-mass spectrometry (LC-MS) analysis. Peptide fragments from AmoA were the predominant peptides detected in 17OD-treated samples. In-gel digestion and matrix-assisted laser desorption ionization-tandem time of flight (MALDI-TOF/TOF) analyses also confirmed that the fluorescent 28-kDa polypeptide was AmoA.


Subject(s)
Nitrosomonas europaea/enzymology , Oxidoreductases/analysis , Proteome/analysis , Aerobiosis , Ammonia/metabolism , Chromatography, Liquid , Mass Spectrometry , Nitrosomonas europaea/chemistry , Oxygen/metabolism
7.
Res Dev Disabil ; 45-46: 261-70, 2015.
Article in English | MEDLINE | ID: mdl-26280691

ABSTRACT

We have previously reported beneficial effects of acute (i.e., single session) Assisted Cycling Therapy (ACT) on manual dexterity and cognitive planning ability in adolescents with Down syndrome (DS). In the present study, we report the chronic effects of eight weeks of ACT, voluntary cycling (VC), and no cycling (NC), on the same measures in adolescents with DS. Participants completed 8 weeks of ACT, VC, or NC. Those in the ACT and VC groups completed 30min sessions three times per week on a stationary bicycle. During ACT, the mechanical motor of the bicycle augmented the cadence to a rate which was on average 79% faster than the voluntary cadence. During VC, the participants pedaled at a self-selected rate. Unimanual dexterity scores as measured with the Purdue Pegboard test (PPT) improved significantly more for the ACT and VC groups compared to the NC group. ACT lead to greater improvements than VC and NC in the assembly sub-test, which is a task that requires more advanced temporal and spatial processing. The ACT group improved significantly more than the VC group and non-significantly more than the NC group in cognitive planning ability as measured by the Tower of London test (ToL). There were also significant correlations between the assembly subtest of the PPT and all measures of the ToL. These correlations were stronger during post-testing than pre-testing. Pre-post changes in the combined PPT score and ToL number of correct moves correlated positively in the ACT group. These results support the efficacy of the salutary effects of ACT on global fine motor function and executive function in DS. Additionally, the performance on complex bimanual dexterity tasks appears to be related to the capacity of cognitive planning ability. This research has important implications for persons with movement deficits that affect activities of daily living.


Subject(s)
Bicycling , Cognition , Down Syndrome/rehabilitation , Exercise Therapy/methods , Motor Skills , Adolescent , Down Syndrome/physiopathology , Down Syndrome/psychology , Executive Function , Female , Humans , Male , Neuropsychological Tests , Young Adult
8.
Science ; 330(6003): 479-82, 2010 Oct 22.
Article in English | MEDLINE | ID: mdl-20966246

ABSTRACT

Diviner Lunar Radiometer Experiment surface-temperature maps reveal the existence of widespread surface and near-surface cryogenic regions that extend beyond the boundaries of persistent shadow. The Lunar Crater Observation and Sensing Satellite (LCROSS) struck one of the coldest of these regions, where subsurface temperatures are estimated to be 38 kelvin. Large areas of the lunar polar regions are currently cold enough to cold-trap water ice as well as a range of both more volatile and less volatile species. The diverse mixture of water and high-volatility compounds detected in the LCROSS ejecta plume is strong evidence for the impact delivery and cold-trapping of volatiles derived from primitive outer solar system bodies.


Subject(s)
Moon , Cold Temperature , Extraterrestrial Environment , Ice , Radiometry , Spectrophotometry, Infrared
9.
Liver Int ; 30(10): 1490-504, 2010 Nov.
Article in English | MEDLINE | ID: mdl-20825557

ABSTRACT

BACKGROUND & AIMS: MicroRNAs (miRNAs) are members of a class of small noncoding functional RNAs that modulate gene regulation at the post-transcriptional level in a sequence specific manner. miRNA dysfunction has been linked to the pathophysiology of human diseases including those resulting from viral infections. The objective of this study was to investigate changes in miRNA profiles that occur in hepatoma cells expressing hepatitis C virus (HCV) and identify anticorrelated mRNAs, which may be their regulatory targets. METHODS: Microarrays were used to perform global miRNA and mRNA expression analysis. Fold changes and pairwise statistics were computed for the resulting datasets. Hierarchical cluster and pathway analyses were performed to assess the degree of differential expression and identify regulatory networks. Bioinformatics tools were used to integrate mRNA profiling results with miRNA target predictions. RESULTS: Replication of the Con1 strain of HCV virus in hepatoma cells elicited extensive differential expression of both miRNAs and mRNAs. Forty-three differentially expressed miRNAs (P≤0.001) were identified by microarray analysis in HCV expressing cells. Six thousand eight hundred and fifteen differentially expressed mRNAs (P≤0.05) were identified. Computational analyses revealed anticorrelated miRNA:mRNA pairs for each target prediction algorithm used. Pathway analysis generated a filtered pathway with 120 entities, including seven major regulators and nine major targets potentially under the control of at least 11 miRNAs. CONCLUSIONS: The expression of a number of anticorrelated miRNAs:mRNA pairs are affected by the presence of HCV. These miRNAs and their putative targets are attractive candidates for being involved in the pathogenesis and/or progression of HCV-induced chronic hepatitis.


Subject(s)
Carcinoma, Hepatocellular/genetics , Gene Expression Profiling , Hepacivirus/pathogenicity , Hepatitis C, Chronic/genetics , Liver Neoplasms/genetics , MicroRNAs/metabolism , RNA, Messenger/metabolism , Algorithms , Carcinoma, Hepatocellular/virology , Cell Line, Tumor , Cluster Analysis , Computational Biology , Gene Expression Profiling/methods , Gene Expression Regulation , Gene Regulatory Networks , Humans , Liver Neoplasms/virology , Oligonucleotide Array Sequence Analysis , Reverse Transcriptase Polymerase Chain Reaction , Transfection
10.
J Surg Res ; 159(1): 456-61, 2010 Mar.
Article in English | MEDLINE | ID: mdl-19786282

ABSTRACT

BACKGROUND: To determine if physical examination can reliably detect or exclude abdominal or pelvic injury in adult trauma activation patients. METHODS: Trauma registry and medical record data were retrospectively reviewed for all adult blunt trauma patients with Glasgow coma scale score>8, from 6/30/05 to 12/31/06. Attending surgeons' dictated admission history and physical examination reports were individually reviewed. Patients' subjective reports of abdominal pain were recorded as present or absent. Exam findings of the lower ribs, abdomen, and pelvis were each separately recorded as positive or negative, and were compared with findings on a subsequent objective evaluation of the abdomen (OEA). "Clinically significant" injuries were defined as those that would change patient management. RESULTS: One thousand six hundred sixty-three patients were studied. Of patients with a negative abdominal exam, 10% had a positive OEA. When abdominal pain was absent, and exam of the lower ribs, abdomen, and pelvis was normal, OEA was positive in 7.6%, and 5.7% had a clinically significant injury. While a positive abdominal exam was predictive of a positive OEA (P<0.01), a negative exam, even when broadened (pain, lower ribs, abdomen, pelvis) did not exclude significant injuries. CONCLUSION: Ten percent of trauma activation patients with a negative abdominal exam have occult abdominal/pelvic injuries. Even when exam of the lower ribs, abdomen, and pelvis are all negative and abdominal pain is absent, 5.7% have occult injuries that would change management. OEA should be used liberally for adult blunt trauma activation patients regardless of physical exam findings, to avoid missing clinically significant injuries.


Subject(s)
Abdominal Injuries/diagnosis , Mass Screening/methods , Physical Examination , Adult , Female , Humans , Male , Retrospective Studies , Trauma Centers
11.
Cancer Invest ; 26(10): 990-8, 2008 Dec.
Article in English | MEDLINE | ID: mdl-19093257

ABSTRACT

Utilizing microarray gene expression data in cancer research possesses the ability to identify deregulated cellular pathways involved in malignant development. This study investigated the relationships of three gene families, HOX, ErbB and IGFBP, with regard to the development of ovarian cancer. These families were of interest because of similar chromosomal locations and their deregulated expression in ovarian cancer. Higher level statistics were used to differentially analyze microarray data in 65 ovarian samples to assess correlation and relationships among the gene families of interest. Fifteen genes in the three families were found to be significantly deregulated. Thirty-eight significant correlations were found within and between the genes of interest. Our data indicates that the significantly modeled relationships between HOX, ErbB and IGFBP gene pairs could provide insight into the underlying biological mechanisms in ovarian cancer.


Subject(s)
ErbB Receptors/genetics , Gene Expression Regulation, Neoplastic , Homeodomain Proteins/genetics , Insulin-Like Growth Factor Binding Proteins/genetics , Ovarian Neoplasms/genetics , Female , Humans , Multigene Family , Oligonucleotide Array Sequence Analysis , RNA, Neoplasm/genetics , RNA, Neoplasm/isolation & purification , Reverse Transcriptase Polymerase Chain Reaction
12.
Plant Physiol ; 148(1): 89-96, 2008 Sep.
Article in English | MEDLINE | ID: mdl-18633120

ABSTRACT

Oilseeds are the main source of lipids used in both food and biofuels. The growing demand for vegetable oil has focused research toward increasing the amount of this valuable component in oilseed crops. Globally, soybean (Glycine max) is one of the most important oilseed crops grown, contributing about 30% of the vegetable oil used for food, feed, and industrial applications. Breeding efforts in soy have shown that multiple loci contribute to the final content of oil and protein stored in seeds. Genetically, the levels of these two storage products appear to be inversely correlated with an increase in oil coming at the expense of protein and vice versa. One way to overcome the linkage between oil and protein is to introduce a transgene that can specifically modulate one pathway without disrupting the other. We describe the first, to our knowledge, transgenic soy crop with increased oil that shows no major impact on protein content or yield. This was achieved by expressing a codon-optimized version of a diacylglycerol acyltransferase 2A from the soil fungus Umbelopsis (formerly Mortierella) ramanniana in soybean seed during development, resulting in an absolute increase in oil of 1.5% (by weight) in the mature seed.


Subject(s)
Diacylglycerol O-Acyltransferase/metabolism , Genes, Fungal , Glycine max/metabolism , Mucorales/genetics , Seeds/metabolism , Soybean Oil/biosynthesis , Agriculture , Diacylglycerol O-Acyltransferase/genetics , Phenotype , Plants, Genetically Modified/genetics , Plants, Genetically Modified/metabolism , Seeds/growth & development , Glycine max/genetics , Glycine max/growth & development
13.
Eur J Cancer Prev ; 16(2): 130-41, 2007 Apr.
Article in English | MEDLINE | ID: mdl-17297389

ABSTRACT

This study examined whether suppression of mammary gland carcinogenesis elicited by low doses of tamoxifen (TAM) can be enhanced by concomitant treatment of rats with indole-3-carbinol (I3C), a component of cruciferous vegetables and a dietary supplement used for its putative antiestrogenicity. Two weeks after one oral dose of 7,12-dimethylbenz[a]anthracene (DMBA) at 65 mg/kg body weight, female Sprague-Dawley rats started treatment with TAM (10 microg/rat) by subcutaneous injection, I3C (250 mg/kg body weight) by oral gavage, TAM+I3C or their respective vehicles three times per week, for up to 20 weeks. Significant increases in the median latency of malignant mammary tumors and decreases in the mean tumor mass per rat were due to TAM. Significant decreases in the mean tumor number per rat in TAM, I3C and TAM+I3C-treated rats indicated a cooperative effect of the two compounds. In both DMBA-initiated and uninitiated rats, significant increases in the ratios of liver to body weight in I3C and TAM+I3C-treated groups coincided with I3C-dependent increases of hepatic cytochrome P450 levels and activities (1A1, 1A2 and 2B1/2). The ratios of uterus to body weight decreased with the number of treatments and the decreases effected by TAM were greater than those by I3C. The levels of circulating estrone were increased in response to I3C treatment and were greater in DMBA-initiated rats than in uninitiated rats, which may contribute to the preventive effect of I3C. Chemoprevention may be accomplished through up-regulation of apoptotic enzyme (caspase) activities in the mammary gland or mammary tumors. Treatment with TAM, I3C or TAM+I3C had no effect on caspase-3&7, caspase-6, caspase-8 and caspase-9 activities in the mammary tumors or mammary gland of tumor-bearing rats or that of uninitiated rats. In the mammary gland of DMBA-initiated tumor-free rats, however, I3C treatment increased the levels of caspase-3&7 and caspase-9 activities, suggesting an I3C-mediated protective effect. Even though I3C alone is a much less effective suppressing agent of mammary carcinogenesis than TAM, I3C in combination with TAM does not weaken but may foster the benefits of chemoprevention with TAM.


Subject(s)
Anticarcinogenic Agents/therapeutic use , Indoles/therapeutic use , Mammary Neoplasms, Animal/prevention & control , Tamoxifen/therapeutic use , Animals , Drug Therapy, Combination , Female , Rats , Rats, Sprague-Dawley
14.
J Exp Bot ; 58(6): 1281-90, 2007.
Article in English | MEDLINE | ID: mdl-17308329

ABSTRACT

Cell wall disassembly in ripening fruit is highly complex, involving the dismantling of multiple polysaccharide networks by diverse families of wall-modifying proteins. While it has been reported in several species that multiple members of each such family are expressed in the same fruit tissue, it is not clear whether this reflects functional redundancy, with protein isozymes from a single enzyme class performing similar roles and contributing equally to wall degradation, or whether they have discrete functions, with some isoforms playing a predominant role. Experiments reported here sought to distinguish between cell wall-related processes in ripening melon that were softening-associated and softening-independent. Cell wall polysaccharide depolymerization and the expression of wall metabolism-related genes were examined in transgenic melon (Cucumis melo var. cantalupensis Naud.) fruit with suppressed expression of the 1-aminocyclopropane-1-carboxylate oxidase (ACO) gene and fruits treated with ethylene and 1-methylcyclopropene (1-MCP). Softening was completely inhibited in the transgenic fruit but was restored by treatment with exogenous ethylene. Moreover, post-harvest application of 1-MCP after the onset of ripening completely halted subsequent softening, suggesting that melon fruit softening is ethylene-dependent. Size exclusion chromatography of cell wall polysaccharides, from the transgenic fruits, with or without exogenous ethylene, indicated that the depolymerization of both pectins and xyloglucans was also ethylene dependent. However, northern analyses of a diverse range of cell wall-related genes, including those for polygalacturonases, xyloglucan endotransglucosylase/hydrolases, expansin, and beta-galactosidases, identified specific genes within single families that could be categorized as ethylene-dependent, ethylene-independent, or partially ethylene-dependent. These results support the hypothesis that while individual cell wall-modifying proteins from each family contribute to cell wall disassembly that accompanies fruit softening, other closely related family members are regulated in an ethylene-independent manner and apparently do not directly participate in fruit softening.


Subject(s)
Cell Wall/physiology , Cucumis melo/physiology , Ethylenes/metabolism , Fruit/physiology , Cucumis melo/genetics , DNA Primers , Ethylenes/biosynthesis , Fruit/genetics , Plants, Genetically Modified/physiology , Pollen/physiology , Polymerase Chain Reaction
15.
Cancer Detect Prev ; 29(4): 338-47, 2005.
Article in English | MEDLINE | ID: mdl-16054776

ABSTRACT

BACKGROUND: Mechanisms underlying prevention by beta-naphthoflavone (beta-NF) of mammary carcinogenesis initiated with 7,12-dimethylbenz[a]anthracene (DMBA) in the rat were elucidated. METHODS AND RESULTS: Treatment of female Sprague-Dawley rats with beta-NF at 40 mg/kg b.wt. for 4 days by oral gavage in corn oil before a single oral dose of DMBA (112 mg/kg b.wt.) suppressed mammary gland carcinogenesis as shown by an increase in the median latent period from 10 to 24 weeks and a 60% decrease in the multiplicity of mammary adenocarcinomas. In contrast, a 20-day treatment with beta-NF starting 3 weeks after DMBA had no significant effects on mammary tumorigenesis. The activities of phase I and phase II enzymes were examined in the liver and mammary gland 24 h after treatment of rats with beta-NF, DMBA, or beta-NF followed by DMBA as in the first bioassay. Treatment with either beta-NF or DMBA increased the hepatic activities of cytochrome P450 (CYP)1A1, 1A2, and 2B1/2, and glutathione S-transferase, and the mammary activity of CYP1A1. The activity of mammary CYP2B1/2 induced by DMBA was decreased by beta-NF. In the liver, the increase of UDP-glucuronosyl transferase (GT) activity in rats treated with beta-NF and DMBA was 2.3-fold greater than in rats treated with DMBA alone. Thus, treatment with beta-NF likely increased the rate of glucuronidation of DMBA dihydrodiols leading to carcinogen detoxification. The levels of the DMBA adducts determined by 32P-postlabeling of the mammary gland DNA were decreased in the beta-NF-pretreated rats. CONCLUSION: The beta-NF-induced increase in the hepatic UDP-GT activity and decrease in the mammary DNA-DMBA adducts occurred under the same treatment regimen that led to suppression of DMBA-induced mammary carcinogenesis.


Subject(s)
9,10-Dimethyl-1,2-benzanthracene/analogs & derivatives , 9,10-Dimethyl-1,2-benzanthracene/antagonists & inhibitors , Adenocarcinoma/prevention & control , Carcinogens/antagonists & inhibitors , DNA Adducts/drug effects , Enzyme Inhibitors/pharmacology , Mammary Glands, Animal/drug effects , Mammary Neoplasms, Experimental/prevention & control , beta-Naphthoflavone/pharmacology , Adenocarcinoma/chemically induced , Animals , Cytochrome P-450 Enzyme System/drug effects , Disease Models, Animal , Enzyme Induction/drug effects , Enzyme Inhibitors/administration & dosage , Female , Glucuronosyltransferase/drug effects , Glutathione Transferase/drug effects , Liver/drug effects , Liver/enzymology , Mammary Neoplasms, Experimental/chemically induced , Rats , Rats, Sprague-Dawley , beta-Naphthoflavone/administration & dosage
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