bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sodium butyrate differentially modulates plasminogen activator inhibitor type‐1, urokinase plasminogen activator, and its receptor in a human colon carcinoma cell
Authors: Reeder Jennifer A. , Dickinson Joanne L. , Chenevix‐Trench Georgia , Antalis Toni M. 
Published: February 2006

AbstractHuman colonic epithelium is exposed to varying levels of sodium butyrate, which is derived from the bacterial fermentation of dietary carbohydrate. Sodium butyrate has several effects on colonic tumor cells in vitro, including arrest of cell growth and differentiation. In the present study we have found that, in addition to a reduction in cellular proliferation, sodium butyrate induces the transient expression of plasminogen activator inhibitor type‐1 (PAI‐1) in the LIM 2405 human colonic tumor cell. Approximately 40% of the PAI‐1 secreted is biologically active as judged by the formation of higher molecular weight, SDS‐resistant complexes with urokinase plasminogen activator (uPA). The enhanced PAI‐1 biosynthesis was accompanied by an increase in PAI‐1 mRNA levels. During the same time period, the amount of secreted uPA remained relatively constant, but the level of cell associated uPA decreased slowly and was accompanied by a decrease in uPA mRNA levels. The uPA receptor is synthesized constitutively by these cells, and was down‐regulated at both the protein and mRNA levels in response to sodium butyrate. The results demonstrate that sodium butyrate can alter the balance of components of the plasminogen activator system in a manner which favours net decreased plasminogen activator activity and suggests a role for sodium butyrate in the regulation of extracellular proteolysis. ©1993 Wiley‐Liss, Inc.
Predicting rodent carcinogenicity of halogenated hydrocarbons by in vivo biochemical parameters
Authors: Kitchin Kirk T. , Brown Janice L. , Kulkarni Arun P. 
Published: February 2006

AbstractForty halogenated hydrocarbons of known rodent carcinogenicity (24 carcinogens, 16 noncarcinogens), including many promoters of carcinogenesis, nongenotoxic carcinogens, and hepatocarcinogens, were selected for study. The chemicals were administered by gavage in two dose levels to female Sprague‐Dawley rats. The effects of these 40 chemicals on four biochemical assays [hepatic DNA damage by alkaline elution (DD), hepatic ornithine decarboxylase activity (ODC), serum alanine aminotransferase activity (ALT), and hepatic cytochrome P‐450 content (P450)] were determined.Composite predictive parameters are defined as follows: CP = [ODC and P450], CT = [ALT and ODC], and TS = [DD or CP or CT]. The operational characteristics of TS for predicting rodent cancer were sensitivity 58%, specificity 81%, positive predictivity 82%, negative predictivity 57%, and concordance 68%. The concordance for the Ames test (45%) and structural alerts (SA; 46%) was much lower. TS also outperformed the Ames test and SA in producing fewer false positives (the specificity of TS was 81% vs. only 63% for the h e s test and 57% for SA). For predicting the carcinogenicity of the most difficult halogenated hydrocarbons (Ames and SA negative chemicals), TS was capable of success‐ fully predicting the carcinogenicity of 8 (carbon tetrachloride, chloroform, α‐hexachloro‐cyclohexane, kepone, mirex, monuron, p,p′‐DDE, and 2,4,6‐trichloropheno1) out of 16 of these non‐DNA‐reactive halogenated hydrocarbon carcinogens. All 8 of these halogenated hydrocarbons were positive in either CP or CT. This evidence shows that nongenotoxic carcinogenesis is best predicted by nongenotoxic parameters such as CP or CT (components of the predictor TS). ©1993 Wiley‐Liss, Inc.This article is a US Government work and, as such, is in the publi domain in the United States of America.
Perspective on the usefulness of the mouse lymphoma assay as an indicator of a genotoxic carcinogen: Ten compounds which are positive in the mouse lymphoma assay but are not genotoxic carcinogens
Authors: Caldwell John 
Published: February 2006

AbstractThe mouse lymphoma assay is commonly included in batteries of tests for the mutagenic and carcinogenic potential of chemicals. Unlike other bacterial and mammalian cell tests, it has an unacceptably high incidence of false positive results. This paper reviews data on ten chemicals, all of which are positive in the mouse lymphoma assay but negative in all other genotoxicity tests. Three are non‐genotoxic rodent carcinogens acting through a variety of secondary mechanisms, while seven are not carcinogenic. It is concluded that a positive mouse lymphoma assay alone cannot be a barrier to the human use of drugs and other chemicals. ©1993 Wiley‐Liss, Inc.
Modification of antigen expression in human and hamster pancreatic cancer cell lines induced by sodium butyrate
Authors: Corra Stefano , Kazakoff Katherine , Mogaki Masatoshi , Cano Martin , Pour Parviz M. 
Published: February 2006

AbstractThe effects of sodium butyrate (NaB) on the growth, morphology, and expression of blood group A, Lewisa, and CA 19‐9 antigen in the hamster pancreatic cancer cell lines, PC‐1 (well differentiated) and PC‐1.0 (poorly differentiated), and of blood group A, DU‐PAN‐2, and CA 19‐9 antigens in four human pancreatic cancer cell lines, HPAF and CD11 (well differentiated) and CD18 and PANC‐1 (poorly differentiated), were examined. NaB inhibited the growth of all cell lines and induced cell enlargement, an increase in secretory material, microfilaments, and pseudopodia. NaB stimulated the production of blood group A antigen in PC‐1.0 cells dose dependently, but no change in the expression of this antigen was observed in the human cell lines. However, NaB treatment increased the presence of cells positive for CA 19‐9 in PANC‐1 but not in the remaining cell lines, none of which reacted with the anti‐CA 19‐9 antibody before or after NaB treatment. Untreated PANC‐1 cells did not produce either blood group A or DU‐PAN‐2 antigen, but expressed these antigens after NaB treatment in a dose‐dependent manner. The results suggest that NaB stimulates the differentiation of the hamster and human pancreatic cancer cell lines and increases or induces the expression of some tumor‐associated antigens. ©1993 Wiley‐Liss, Inc.
Sequencing analysis of Ha‐, Ki‐, and N‐ras genes in rat urinary bladder tumors induced by N‐[4‐(5‐nitro‐2‐furyl)‐2‐thiazolyl]formamide (FANFT) and sodium saccharin
Authors: Masui T. , Mann A. M. , Borgeson C. D. , Garland E. M. , Okamura T. , Fujii H. , Pelling J. C. , Cohen S. M. 
Published: February 2006

AbstractMale F344 rats were fed N[4‐(5‐nitro‐2‐furyl)‐2‐thiazolyl]formamide (FANFT) for up to 4 wk, then given the basal diet with or without 5% sodium saccharin for up to 100 wk. In a previous study, we demonstrated point mutations in codons 12 and 61 of Ha‐ras gene among eleven transitional cell carcinomas (TCC), one undifferentiated carcinoma, and two sarcomas of the urinary bladder (Mol Carcinogen 3:210–215, 1990). In this study, Ha‐ras, Ki‐ras, and N‐ras sequences were examined by polymerase chain reaction (PCR) and direct DNA sequencing. The results confirm the point mutation in codon 61 (CAA to CGA in 5 TCCs and to CTA in one TCC) of the Ha‐ras gene. Mutation at codon 12 was not confirmed. No mutation was found in the Ki‐ras gene. Sequences of the N‐ras gene exons 1 and 2 were determined, and no mutations was detected. These results suggest the involvement of activated Ha‐ras gene, but not Ki‐N or N‐ras gene, in rat urinary bladder carcinogenesis induced by FANFT. Subsequent sodium saccharin administration did not affect the changes in Ha‐ras gene. ©1993 Wiley‐Liss, Inc.
Cytosine attack by free radicals arising from bromotrichloromethane in the presence of benzoyl peroxide catalyst: A mass spectrometric study
Authors: Castro G. D. , Castro J. A. 
Published: February 2006

AbstractWe and others previously reported that CCl4 reactive metabolites are able to covalently bind to liver DNA either in vivo or in vitro. However, no demonstration of the structure of resulting adducts is available in literature. That information would be of relevance, for CCl4 exhibits null or contradictory mutagenic properties and is currently considered a non‐genotoxic carcinogen.In the present study we report the nature of the reaction products formed when the putative CCl4 metabolites, ·CCl3 and CCl3O2· attack cytosine in a purely chemical system where they were generated from CCl3Br in a benzoyl peroxide catalyzed reaction.Reaction products formed and identified were a) under nitrogen (·CCl3 present)—5‐bromo cytosine and cytosine‐5‐carboxylic acid; b) under air (CCl3O2· present)—5‐bromo cytosine, 5‐chloro cytosine, 5‐hydroxy cytosine, 6‐hydroxy cytosine (tentative), chloro hydroxy uracil, 5,6‐dihydroxy uracil, and chloro trichloromethyl cytosine.Results from present experiments suggest that if these reaction products were also produced in vivo during either CCl4 or CCl3Br poisoning and they were not repaired in due time prior to replication, they would lead to mutagenic events. Studies directed to obtain evidence for their in vivo formation are in course in our laboratory. ©1993 Wiley‐Liss, Inc.
Comparative kinetic studies on aflatoxin B1 binding to pulmonary and hepatic DNA of rat and hamster receiving the carcinogen intratracheally
Authors: Biswas Gopa , Raj Hanumantharao G. , Allameh Amir , Saxena Manju , Srivastava Narender , Mukerji Krishna G. 
Published: February 2006

AbstractSeveral epidemiological studies have discussed the outcome of inhalation of airborne aflatoxins by humans. Metabolism of aflatoxin B1 (AFB1) by lung parenchyma leading to DNA binding is reported here. The tissue distribution pattern of [3H]AFB1 radioactivity revealed the lungs to be the second most important organ after the liver to retain a considerable amount of the radioactivity (66%). The lung indicated a selective activation of AFB1 as it showed only 7.7% binding of [3H]AFB1 to pulmonary DNA. Rats and hamsters were dosed with [3H]AFB1 (2 μCi containing 40 μg AFB1/100 g body wt.) intratracheally (i.t.) and sacrificed at different intervals after toxin treatment. Peak binding occurred at 0.5, 1, and 2 h in case of hamster lung, rat lung, and alveolar macrophages of both the species, respectively. At the end of 24 h, the relative AFB1‐DNA binding (percentage of peak binding) in hamster lung was 72% while that in rat was 24%. The relative binding in rat lung alveolar macrophages (AMs) was generally higher than that of the hamster. AFB1 binding to hepatic DNA of both the species approached the peak at 1 h after the toxin administration i.t. Under these conditions, binding of AFB1 (or its metabolites translocated to liver) to hepatic DNA of both the species progressively diminished with time in contrast to lung, as revealed by the relative binding values at 12 h for rat and hamster lung, which were 48 and 67%, respectively, while for the rat and hamster liver they were 28 and 24%, respectively. Binding of i.t. administered [3H]AFB1 to rat liver DNA is only marginally higher than that observed with hamster liver, in contrast to the wide difference observed in animals receiving AFB1 intraperitoneally. These results highlight the persistence of AFB1 binding to pulmonary DNA, and the extent of translocated AFB1 binding to hepatic DNA presents an interesting difference from that observed when the toxin was administered through a gastrointestinal route. It is worth concluding that AMs unlike many other xenobiotics, possess specific mixed function oxidase activity to epoxidize AFB1. ©1993 Wiley‐Liss, Inc.
DNA alkyation and mutagenicity of related hydroxypropylating and methylating agents in V79 cells
Authors: Lawson Terence , Gannett Peter 
Published: February 2006

AbstractN‐Nitrosobis (2‐hydroxypropyl) amine (BHP) and N‐nitrosobis (2‐oxopropyl) amine (BOP) require metabolism to be carcinogenic and mutagenic. This metabolism produces hydroxypropylating and methylating alkylating species. To measure the effects of these species, we compared the action of direct‐acting model compounds that are hydroxypropylating or methylating agents with those of BHP and BOP. Mutagenicity in V79 cells and the alkylation of V79 cell DNA were measured. The model compounds were ethyl‐N‐nitroso (2‐oxopropyl) carbamate (NOPC), a methylating agent, and its 2‐hydroxypropyl congener (NHPC), a hydroxypropylating agent. BHP and BOP were metabolized by hepatocytes from male Syrian hamsters. At the highest dose (2 mM) BOP produced 12 times more mutants than BHP but only 2.5 times more O6methylguanine (O6MeG) than BHP. When a pancreas duct homogenate was used, 87 (BOP) and six (BHP) mutants/106 survivors were measured. When hepatocytes (not a homogenate) were used to metabolize BOP, 351 μmol O6MeG/mol guanine (G) and 39 μmol O6 (2‐hydroxypropyl) G (O6HpG)/mole G were found in V79 DNA. When a pancreas duct homogenate was used BHP produced O6HpG (65 μmol/mol G) and BOP O6MeG (20 μmol/mol G). NOPC produced five times more mutants than NHPC, over the range of doses. At the highest dose (10 μM) it produced less (70%) O6alkylG than NHPC. These data show that methylation was a more mutagenic lesion than hydroxypropylation. There was no evidence of a correlation between mutagenicity and the formation of O6alkylG. ©1993 Wiley‐Liss, Inc.
Stability of microsomal monooxygenases in murine liver S9 fractions derived from phenobarbital and β‐naphthoflavone induced animals under various long‐term conditions of storage
Authors: Bauer Carlo , Corsi Claudio , Paolini Moreno 
Published: February 2006

AbstractThe aim of this study was to define the long‐term stability of metabolizing enzymes in activating preparations for short‐term genotoxicity bioassays under various storage conditions. Expressions of cytochrome P450 content, NADPH‐cytochrome (P450) c‐re‐ductase activity, and of the several monooxygenases, such as aminopyrine N‐demethylase (class IIIA P450), p‐nitroanisole O‐demethylase (mixed), dinemorphan N‐demethylase (HB1), ethoxyresorufin O‐deethylase (IA1), ethoxycoumarin O‐deethylase (mixed), and pentoxyresorufin O‐dealkylase (IIB1), were examined in S9 fractions derived from Na‐phenobarbital (PB) plus β‐naphthoflavone (β‐NF) induced male and female mice, stored at −80°C, or lyophilized and stored at −20°C. Lipid peroxidation was also determined. Cytochrome P450 and the associated activities were decreased by 30–82% within 9 months of storage. The pattern and degree of relative stabilities were different for the various isoforms. The IA 1‐like activity, for example, was much more stable (˜49%loss) than IIB 1‐like activities (up to 82% loss). In general, lyophilized enzymes were less stable than directly frozen preparations. In addition, immediately after freeze‐drying (lyophilization), a marked decrease in activity of up to 35% was observed. On the contrary, demethylation of aminopyrine and p‐nitroanisole remains almost constant over 6 months storage at −196°C. The results obtained indicate that either fresh, daily made S9 fractions or, alternatively, fractions stored in liquid nitrogen (up to 6 months) are recommended for mutagenesis studies. © 1994 Wiley‐Liss, Inc.
Taxol and embryonic development in the chick
Authors: Scialli Anthony R. , Desesso John M. , Goeringer Gerald C. 
Published: February 2006

AbstractTaxol, an inhibitor of microtubule disassembly, is currently under investigation in the therapy of several human cancers. The current investigation was undertaken to characterize potential taxol developmental toxicity in chicks. On one of days 1–4 of incubation, taxol was administered in dimethylsulfoxide (DMSO) or olive oil in a range of doses, the highest of which produced a high incidence of early embryo death. Production of gross structural malformations was sporadic and occurred in vehicle‐treated as well as taxol‐treated embryos. A more common manifestation of taxol toxicity was a syndrome of visceral abnormalities, including regression of the vitelline circulation, dilatation of the atria, and hemorrhage in the left side of the head and thorax, often with decreased eye pigmentation. Regardless of the day of treatment, this syndrome occurred at 4.5–5 days. To investigate the possibility that taxol induced its effect through disruption of angiogenesis in the vitelline circulation, filters soaked in taxol were applied to the margin of the germ disc. No inhibition of vessel development was demonstrated. We conclude that taxol decreases the viability of embryos and that this impairment of survival precludes the development of birth defects. Solvent toxicity is an important confounder in the investigation of taxol embryotoxicity. © 1994 Wiley‐Liss, Inc.
Induction of structural chromosome aberrations in human lymphocyte cultures and CHO cells by permethrin
Authors: Barrueco Carmen , Herrera Angustias , Caballo Covadonga , de la Peña Eduardo 
Published: February 2006

AbstractThe pyrethroid insecticide permethrin was tested for its ability to induce structural chromosome aberrations (CA) in human lymphocyte cultures and CHO cells, in order to confirm the clastogenic effect of itself and to compare the response of the two different cell types. Permethrin was tested in the range of 50–200 μg/ml in human lymphocyte cultures and in the range of 20–100 μg/ml in CHO cells. In both lymphocyte and CHO cultures, assays were performed in the absence and in the presence of a rat liver activation system (S9 mix). In the absence of S9 mix, two experiments with different duration of the treatment were carried out. Permethrin induced CA in both cultures when it was evaluated in the absence of a metabolic activation system. The activity of a given concentration of permethrin seemed to be decreased more by the reduction of the time of exposure than by the presence of S9 mix. Aberrations induced by permethrin were mainly chromosome‐type aberrations in both cultures. Thus, permethrin can be characterised as an S‐phase independent clastogenic agent. The response of both lymphocyte and CHO cultures was similar, indicating that both systems showed the same sensitivity for detecting the clastogenicity in vitro of permethrin. © 1994 Wiley‐Liss, Inc.
Preferential pericentric lesions and aneuploidy induced in mouse oocytes by the topoisomerase II inhibitor etoposide
Authors: Mailhes John B. , Marchetti Francesco , Phillips George L. , Barnhill Danny R. 
Published: February 2006

AbstractEtoposide (VP‐16) is used as an antineoplastic drug in humans. It inhibits topoisomerase II (topo II) activity by forming a ternary complex (DNA‐etoposide‐topo II). This complex prevents the DNA‐strand rejoining activity of topo II, which results in DNA‐strand breaks and the formation of structural chromosome aberrations. Topo II activity is also required for removing regions of DNA catenation prior to chromosome segregation. The possibility exists that patients undergoing etoposide chemotherapy may incur genetic damage and, consequently, may be at a greater risk for developing secondary tumors and having genetically abnormal offspring. We studied the ability of etoposide for inducing both structural chromosome aberrations and aneuploidy in mouse oocytes. Different dosages of etoposide were given to female mice at various times before and after human choronic gonadotrophin injection, and ovulated oocytes were collected 17 h later. The proportions of chromatid acentric fragments and of hyperploid metaphase II oocytes were significantly higher (P < 0.01) in the etoposide groups than in concurrent controls. These results indicate that both structural and numerical aberrations can be induced without direct interaction with DNA or with the various organelles associated with chromosome segregation. Additionally, unlike other compounds (vinblastine, colchicine, benomyl, and griseofulvin) that induce both meiotic delay (ovulated metaphase I oocytes and polyploidy) and aneuploidy, etoposide did not cause meiotic delay in oocyte maturation. © 1994 Wiley‐Liss, Inc.
Changes in secondary structure of DNA of rat embryos following treatment with 1,2‐diethylhydrazine and dimethylnitrosamine in vivo
Authors: Huang Peter H. T. , Catalano Alberto 
Published: February 2006

Abstract1,2‐Diethylhydrazine (DEH) and dimethylnitrosamine (DMN) are indirect acting carcinogens that require metabolic activation to exert their potency. DEH is a transplacental carcinogen and teratogen in Wistar rats when administered by i.p. injection on day 12 of gestation. DMN is embryotoxic during this period. In this study, gravid Wistar rats were injected i.v. with DEH (10, 15, or 20 mg/kg) or i.p. with DMN (10 or 30 mg/kg) and the effects on the embryos 24 hours later were observed. Controls were similarly injected with saline vehicle. The incidence of resorptions increased after treatment with 20 mg DEH/kg. DEH treatment also resulted in decreases in embryo wet weights and total DNA that were not dose dependent. Treatment with DMN did not affect embryonic wet weights and total embryonic DNA amount when compared to the saline‐treated controls. The effects of DEH and DMN on DNA synthesis in vivo were monitored by injecting [methyl‐14C]‐thymidine 1 hour prior to embryo death. DEH induced significant increases in thymidine incorporation into embryo DNA but the increases were not proportional to the doses administered. DNA synthesis was significantly decreased in embryos treated with 30 mg DMN/kg. The DNA of treated and control embryos was fractionated by benzoylated DEAE‐cellulose (BD‐cellulose) chromatography to determine differences in DNA secondary structure following treatment. BD‐cellulose chromatography separates double‐stranded DNA from DNA containing single‐stranded regions by step elution with 1 M NaCl solution and caffeine solution, respectively. Embryonic DNA was monitored by in vivo labelling with [methyl‐3H]‐thymidine on days 6 and 7 of gestation. Significant dose dependent increases in percentages of caffeine‐eluted DNA (%CE‐DNA) compared to controls were detected after treatment with 10, 15, and 20 mg DEH/kg and 10 and 30 mg DMN/kg. The relative %CE‐DNA is expressed as the ratio of %CE‐14C‐labelled DNA to %CE‐3H‐labelled DNA. Litters treated with 10, 15, and 20 mg DEH/kg had relative %CE‐DNA values significantly lower than controls. The results support the hypothesis that initiation mechanisms of transplacental carcinogenesis and teratogenesis are different. The pertinence of %CE‐DNA and relative %CE‐DNA values to the study of transplacental carcinogenesis and teratogenesis is discussed. © 1994 Wiley‐Liss, Inc.