bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative promoting activities of phosphate salts on rat two‐stage bladder carcinogenesis under conditions of equivalent urinary Na+ or K+ Levels
Authors: Shibata Masa‐Aki , Kagawa Masataka , Kawabe Mayumi , Hagiwara Akihiro , Fukushima Shoji 
Published: February 2006

AbstractPromoting effects of Na or K phosphate salts on rat two‐stage bladder carcinogenesis were compared. Animals were treated with 0.05% N‐butyl‐N‐(4‐hydroxybutyl)nitrosamine (BBN) in their drinking water for 4 weeks and thereafter received 1.4% Na3PO4, 2.0% NaH2PO4, 1.0% K3PO4, or 2.5% KH2PO4, these dietary concentrations being selected because they result in approximately equal levels of Na+ and K+ in the urine, equivalent to moderate natriuresis or kaluresis in comparison with our previous data. Treatment with Na3PO4 or K3PO4 induced significant increase in urinary pH compared with control values, whereas urinary pH in the NaH2PO4 and KH2PO4 groups was comparable to control values. With regard to preneoplastic lesion development, both incidences and multiplicity were significantly increased in the groups given Na3PO4 or K3PO4 compared with both controls and NaH2PO4 or KH2PO4 groups, respectively. Furthermore, treatment with Na3PO4 significantly increased multiplicity of papillomas, accompanied by a tendency to increased incidence. No statistically significant difference in promoting potential between Na3PO4 and K3PO4 groups was evident. The present results thus suggest that tumor promotion under conditions of moderate natriuresis or kaluresis depends primarily on high urinary pH. © 1992 Wiley‐Liss, Inc.
Joint action oft‐retinoic and valproic acids onXenopusembryo development
Authors: Dawson Douglas A. 
Published: February 2006

AbstractThe joint action of all‐transretinoic acid (RA) with valproic acid (VPA) was examined at malformation‐inducing concentrations forXenopusembryos. The compounds were selected for testing to evaluate malformation as an endpoint for the developmental toxicity of chemical mixtures and to help assess whether joint action types can be related to modes or mechanisms of chemical toxicity forXenopus.Three mixtures (3:1, 1:1, and 1:3 RA:VPA) were tested in 96 hr static‐renewal exposures. Three separate tests were conducted on each mixture. Positive controls were also tested (i.e., 1:0 and 0:1 solutions). Using toxic unit analysis, the joint action for induction of malformations of all types, craniofacial malformations, and microcephaly was response addition, indicating the chemicals are dissimilar and non‐interactive. The results support recent joint action studies in providing evidence that similar acting chemicals might be defined as chemicals with the same biochemical/molecular mechanism of action in inducing malformations inXenopusembryos. © 1992 Wiley‐Liss, Inc.
Neural tube and other developmental anomalies in the guinea pig following maternal hyperthermia during early neural tube development
Authors: Cawdell‐Smith Judith , Upfold Jeffrey , Edwards Marshall , Smith Murray 
Published: February 2006

AbstractGuinea pigs were exposed to hyperthermia for 1 hr once or twice on day 11, 12, 13, or 14 (E11–E14) of pregnancy. The mean rectal temperatures were elevated by 3.4°C–4.0°C. This treatment resulted in a marked elevation of rates of resorption and developmental defects in embryos examined at day E23. The defects observed were those affecting the neural tube (NTD) (exencephaly, encephaloceles, and microphthalmia), kyphosis/scoliosis, branchial arch defects, and pericardial edema. Embryos with NTD and kyphosis/scoliosis have not been found among newborn guinea pigs to date following maternal heat exposure on days E12–E14. It appears that embryos with these defects are filtered out by resorption or abortion by days E30–E35. © 1992 Wiley‐Liss, Inc.
Modulation of cyclophosphamide mutagenicity by vitamin C in the in vivo rodent micronucleus assay
Authors: Ghaskadbi Surendra , Rajmachikar Savita , Agate Chandana , Kapadi A. H. , Vaidya V. G. 
Published: February 2006

AbstractThe modulatory effect of vitamin C (Vit C) on the mutagenic effect of the antineoplastic drug cyclophosphamide (CP) was assessed in the in vivo micronucleus test in Swiss mice. Simultaneous oral administration of Vit C with i.p. administration of CP was found to decrease the frequency of micronucleated polychromatic erythrocytes elevated by CP. Vit C exhibited a significant antimutagenic effect over a wide dose range (1.56–200 mg/kg). The dose‐response relationship was highly significant. These results demonstrated the ability of the in vivo micronucleus test to detect in vivo modulation of CP mutagenicity by Vit C. Our earlier results and those from other laboratories also indicate that this model system is suitable for primary in vivo screening of modulation of mutagenesis. © 1992 Wiley‐Liss, Inc.
Tobramycin‐induced changes in renal histology of fetal and newborn Sprague‐Dawley rats
Authors: Mantovani A. , Macrì C. , Stazi A. V. , Ricciardi C. , Guastadisegni C. , Maranghi F. 
Published: February 2006

AbstractEffects on renal development were studied using tobramycin (TBM) as a model compound. Pregnant Sprague‐Dawley rats were injected i.p. with TBM at 30 or 60 mg/kg body weight/day on gestational days (GD) 10–19. Kidneys from dams and conceptuses were examined on GD 20 and on postnatal day (PD) 9. The dosing regimen caused in dams moderate proximal tubular alterations and increased concentrations in serum creatinine. Fetal kidneys showed granularity and swelling of proximal tubule cells at the 30 mg/kg dose, poor glomerular differentiation at the 60 mg/kg dose, increased glomerular density at both doses, and no changes on macroscopic examination at either dose. In newborns were observed a moderate developmental delay and tubular lesions at the higher dose, and dose‐related increases of glomerular density and relative medullary area at both doses. All findings were more pronounced in males. A maturational disruption of the tubular structures possibly leading to increased glomerular density was attributed to TBM exposure during renal organogenesis in the rat. © 1992 Wiley‐Liss, Inc.
Teratogenic effects of N‐nitrosodiethylamine in embryos of the hermaphroditic fish Rivulus marmoratus
Authors: Park Eun‐H. , Kim Dong S. , Chang Hwa‐H. 
Published: February 2006

AbstractExposure of N‐nitrosodiethylamine (NDEA) to hermaphroditic fish (Rivulus marmoratus) embryos induced specific congenital malformations when the chemical was applied to embryos on days 0–6 post morula stage. This sensitive period generally coincided with the known period of organogenesis in this species, and the incidence of anomalies was clearly dose related. These results indicate that NDEA is teratogenic to fish embryos. © 1992 Wiley‐Liss, Inc.
A morphologic basis postulated for valproic acid's embryotoxic action in rats
Authors: Khera K. S. 
Published: February 2006

AbstractA tentative 3 phase sequence of pathogenesis is proposed for the embryotoxic action of valproic acid (800 mg/kg) administered orally to rats on day 13 of pregnancy. This is based on histopathological changes in the extraembryonic and embryonic tissues which occurred in the absence of any biologically significant effect on maternal homeostasis. Major events in the first, decidual (or maternal) phase are cells lining the maternal sinusoids in the decidua basalis are necrosed, desquamated, and washed away by the arterial circulation through the afferent channels. The necrosed cells, with their walls still intact, occlude the lumen of these arterial channels at the point of their entry into the giant cell‐trophospongial zone. The channel occlusions cause ischemia and homeostasis of the maternal circulation in the labyrinth by reducing the rate of inflow of maternal blood. The embolic occlusion of maternal arterial channels apparently results in a long‐term reduction in the number and size of maternal channels that supply arterial blood to the labyrinth. In the second or placental phase, the parenchyma of the labyrinth and connective tissue in the chorionic plate and umbilical cord, which have been deprived of nutrition and oxygen by the ischemia and stasis of maternal blood in the labyrinth, undergo degenerative changes. In the third or embryonic phase, a pleiotropic karyorrhexis in the embryo, initiated as early as 4 h postdosing, appeared aggravated, presumably by the preceding labyrinthine degeneration of the placental phase. The valproic acid‐induced embryotoxicity thus seemed to result from a combination of maternal, placental, and embryonic changes. © 1992 Wiley‐Liss, Inc.
Evaluation of the developmental toxicity of trichloroethylene and detoxification metabolites using Xenopus
Authors: Fort Douglas J. , Stover Enos L. , Rayburn James R. , Hull Mendi , Bantle John A. 
Published: February 2006

AbstractPotential mechanisms of trichloroethylene‐induced developmental toxicity were evaluated using FETAX (Frog Embryo Teratogenesis Assay—Xenopus). Early Xenopus laevis embryos were exposed to trichloroethylene for 96 h in two separate definitive concentration‐response assays with and without an exogenous metabolic activation system (MAS) and inhibited MAS. The MAS was treated with either carbon monoxide or cyclohexene oxide to modulate mixed‐function oxidase (MFO) or epoxide hydrolase activity, respectively. Trichloroethylene metabolites: dichloroacetic acid, trichloroacetic acid, trichloroethanol, and oxalic acid were also evaluated in two separate definitive, static renewal tests. Addition of the MAS decreased the 96 h LC50 and EC50 (malformation) of trichloroethylene 1.8‐fold and 3.8‐fold, respectively. Addition of the carbon monoxide inhibited MAS decreased the developmental toxicity of activated trichloroethylene to levels approximating that of the parent compound. Cyclohexene oxide‐inhibited MAS substantially increased the developmental toxicity of trichloroethylene. In addition, each of the metabolites tested were significantly less developmental toxic than the parent compound, trichloroethylene. Results indicate that a highly embryotoxic epoxide intermediate, trichloroethylene oxide, formed as the results of MFO mediated metabolism may play a significant role in the developmental toxicity of trichloroethylene in vitro. ©1993 Wiley‐Liss, Inc.
Embryotoxicity induced by alkylating agents: 7. Low dose prenatal‐toxic risk estimation based on NOAEL risk factor approach, dose‐response relationships, and DNA adducts using methylnitrosourea as a model compound
Authors: Platzek Thomas , Bochert Gerd , Meister Reinhard , Neubert Diether 
Published: February 2006

AbstractPrenatal‐toxic risk estimation for the alkylating model compound methylnitrosourea (MNU) was performed using different procedures. Risk of low doses was estimated using linear extrapolation to zero (estimated ED0.1%: 0.1 mg/kg body wt MNU) as well as extrapolation by probit analysis based on a dose‐response study (estimated ED0.1%: 1.6 mg/kg body wt). Furthermore, a “virtually safe dose” was established by means of the NOAEL risk factor approach (e.g., factor 30: 0.03 mg MNU per kg body wt). In previous studies in murine embryos using MNU, we combined dose‐response data and DNA adduct rate measurements and deduced that O6‐methylguanine is a suitable variable for molecular dosimetry. In a tentative approach, we estimated the teratogenic risk of low doses based on the adduct rates of O6‐methylguanine in the DNA of the embryos. It is concluded that in the case of steep dose‐response relationships, which are typical for the majority of teratogenic effects, the NOAEL risk factor approach is more conservative than extrapolation based on probit analysis. Risk estimation using dosimetry with this model compound yields estimated incidences similar to linear extrapolation. ©1993 Wiley‐Liss, Inc.
Embryotoxicity induced by alkylating agents: 8. DNA adduct formation induced by ethylmethanesulfonate in mouse embryos
Authors: Platzek Thomas , Bochert Gerd , Rahm Ute 
Published: February 2006

AbstractIn previous studies using methylating agents a correlation was found between the initial DNA adduct rate (O6‐methylguanine) in the embryo and the teratogenic efficiency. This was shown by measuring DNA adduct rates in the teratogenic dose range which exhibited similar adduct rates at the equivalent teratogenic dose levels.A similar approach was performed using the ethylating agent ethylmethanesulfonate (EMS). In the teratogenic dose range (150–250 mg/kg bw) the adduct rates of O6‐ethylguanine were similar compared to those of O6‐methylguanine which were obtained with methylating agents. We conclude that a correlation between teratogenicity and adduct rate (O6‐alkylguanine) exists for both methylating and ethylating agents.Furthermore, DNA adduct formation following doses at and below the no‐observed‐adverse‐effect‐level (NOAEL) of teratogenicity was determined. The lowest experimental dose was 45 mg/kg EMS. Substantial DNA adduct rates in the embryos were found. These data will be used for molecular dosimetry in a risk assessment of low doses. © 1994 Wiley‐Liss, Inc.
Antitransforming activity of chlorophyllin against selected carcinogens and complex mixtures
Authors: Wu Z. L. , Chen J. K. , Ong T. , Brockman H. E. , Whong W.‐Z. 
Published: February 2006

AbstractChlorophyllin, a derivative of chlorophyll, is known to be an antimutagenic agent. Studies were performed to determine whether chlorophyllin can also inhibit morphological transformation of BALB/3T3 cells induced by carcinogens and complex mixtures. Chlorophyllin was added to the cultures simultaneously with carcinogens or complex mixtures while the transformation assay was conducted. At concentrations that did not significantly affect cell growth, chlorophyllin was found to inhibit morphological transformation induced by N‐methyl‐N′‐nitro‐N‐nitrosoguanidine, 3‐methylcholanthrene, 7,12‐dimethylbenz(a)anthracene, benzo(a)pyrene, aflatoxin B1, and extracts of coal dust, tobacco snuff, and chewing tobacco. In all cases, the mean number of transformed foci per flask treated with chlorophyllin was significantly lower than that of untreated cultures. The reduction in the number of transformed foci was dependent on the concentration of chlorophyllin tested. These results indicate that chlorophyllin is an antitransforming agent. © 1994 Wiley‐Liss, Inc.
Structural basis for the induction of preneoplastic glutathione S‐transferase positive foci by hepatocarcinogens
Authors: Sakai Toshihisa , Klopman Gilles , Rosenkranz Herbert S. 
Published: February 2006

AbstractA data base consisting of 100 chemicals tested for the ability to enhance the formation of glutathione‐S‐transferase (GST) positive preneoplastic lesions were analyzed by the CASE structure‐activity relational system. A number of structural determinants associated with the induction of GST‐positive foci were recognized. The majority of these describe non‐electrophilic moieties. It is concluded that there is a structural basis for the induction of these neoplastic lesions; interestingly, it was found that this activity is associated with structures that are non‐electrophilic. Reconstruction experiments have indicated that the identified structures are meaningful and that their significance could be better understood with the availability of test results on additional chemicals. © 1994 Wiley‐Liss, Inc.
Morphological transformation induced by glass fibers in BALB/c‐3T3 cells
Authors: Gao H.‐G. , Whong W.‐Z. , Jones W. G. , Wallace W. E. , Ong T. 
Published: February 2006

AbstractStudies were conducted to determine whether (1) glass fibers can induce morphological transformation in BALB/c‐3T3 cells, (2) the transforming activity of glass fibers is related to fiber size, and (3) transformed cells induced by glass fibers possess neoplastic properties. In the transformation assay, BALB/c‐3T3 cells were treated with three different types of glass fibers: Manville code 100 (JM‐100, Manville Corp., Denver, CO), Owens‐Corning AAA‐10 (AAA‐10, Owens‐Corning Corp., Toledo, OH), and Owens‐Corning general building insulation (ISL, Owens‐Corning Corp.) fibers. The neoplastic properties were investigated using the soft agar cloning and gene transfection methods. All three different glass fibers were cytotoxic at high concentrations and induced dose‐related increases in morphological transformation. The transforming activity was inversely related to fiber size, with AAA‐10 showing higher activity than JM‐100 and JM‐100 showing higher activity than ISL fiber. Transformed cells induced by glass fibers exerted anchorage‐independent growth (90%) and DNA transfection‐mediated transformation (100%). These results indicate that glass fibers are capable of transforming mammalian (BALB/c‐3T3) cells in vitro as a function of their physical properties and that glass fiber‐induced transformed cells possess preneoplastic characteristics © 1995 Wiley‐Liss, Inc.This Article is a US Government work and, as such, is in the public domain in the United States of America.
Evaluation of the OECD 421 reproductive toxicity screening test protocol using 1‐(butylcarbamoyl)‐2‐benzimidazolecarbamate (benomyl)
Authors: Piersma A. H. , Verhoef A. , Dortant P. M. 
Published: February 2006

AbstractThe OECD 421 reproductive toxicity screening test protocol was evaluated using the fungicide benomyl as a test compound at 10, 30, or 90 mg/kg per day. Male rats showed dose‐dependent testicular degeneration after 28 days exposure, as expected on the basis of literature data. Dams in the high dose group, exposed from 14 days premating to postnatal day 6, had pups with decreased weights at postnatal days 1 and 6. Prenatal deaths were increased, but no malformations were found. In contrast, in a developmental toxicity test with exposure between gestation days 6 and 15,90 mg/kg induced a high level of postimplantation loss, with ophthalmic malformations in the surviving offspring, in agreement with literature data. It is suggested that premating exposure in the OECD 421 protocol may have induced tolerance to the compound, e.g., by modulation of biotransformation in the dam. These findings indicate that the teratogenic potential of a compound need not necessarily be revealed using this screening test. The OECD 421 protocol appeared sufficiently sensitive to reveal the reproductive hazard of benomyl on the basis of prenatal deaths and testicular and pup weight effects. However, the absence of congenital anomalies in the offspring after benomyl treatment according to the OECD 421 protocol underscores the notion that lack of biological activity in the test should not be regarded as evidence of lack of activity of a compound on reproductive parameters. © 1995 Wiley‐Liss, Inc.
Evaluation of the modifying influence of arecanut on the garlic‐modulated hepatic detoxication system enzymes, sulfhydryl content, and lipid peroxidation in mice
Authors: Singh Anjali , Rao A. R. 
Published: February 2006

AbstractThis paper evaluates the potential effects of arecanut (Areca catechu, L.), an important ingredient of betel quid, on the garlic (Allium sativum, L.)‐modulated activities of hepatic detoxication system enzymes, acid soluble sulfhydryl content, and lipid peroxidation in mice. Mice were fed on either a normal diet or a diet containing 0.25%, 0.5%, or 1% (w/w) arecanut for 45 days. During the last 10 days of treatment oral administration of garlic at the dose level of 20 or 100 mg/kg body weight/day was supplemented. Significant modulation in the activities of phase I and phase II enzymes, –SH content, and malondialdehyde (MDA) level by garlic was observed. Garlic‐modulated alterations in glutathione S‐transferase (GST) activity and –SH content were decreased, while cytochrome b5, cytochrome P‐450, and MDA levels were further augmented by the arecanut plus garlic treatments. © 1995 Wiley‐Liss, Inc.
Influence of high‐fat diets on the occurrence of spontaneous uterine endometrial adenocarcinomas in rats
Authors: Nagaoka Takaharu , Onodera Hiroshi , Hayashi Yuzo , Maekawa Akihiko 
Published: February 2006

AbstractThe effects of high‐fat diets on the spontaneous occurrence of uterine endometrial adenocarcinomas were examined in the Donryu rat. Ninety females at 6 weeks of age were equally divided into 3 groups. Animals in group 1 were fed a basal diet, while those in groups 2 and 3 received powdered basal diets containing 10% and 20% corn oil until 15 months of age, when all survivors were sacrificed. For sequential serum steroid assay and histological examination of sex organs, additional rats were fed diets containing 20% corn oil or without supplement.Body weight gain in group 3 was significantly increased, while in group 2 it was similar to that in the control. In both high‐fat groups, calorie intake and weight of fat deposits in the abdominal cavity were significantly increased. The incidences of uterine adenocarcinomas in groups 2 and 3 were 18% (P < 0.05) and 7%, respectively, as compared to 0% in group 1. Severe hyperplasia (hyperplasia+++) also showed a non‐significant tendency for increase in incidence. In both high‐fat groups, an elevated incidence of persistent estrus was generally observed until 8 months of age. Sequential assays of steroid hormones in rats fed a 20% fat diet showed a tendency for early elevation and continued high values for the serum estrogen: progesterone (E2:P) ratio. In these rats, histological changes in the ovary, uterus, and vagina also appeared at an early stage, as compared to rats fed the basal diet. These results suggest that a high‐fat diet may exert a slight promoting effect on the spontaneous occurrence of uterine adenocarcinomas in Donryu rats, and this might be mechanistically related to hormonal imbalance and a high E2:P ratio in particular. © 1995 Wiley‐Liss, Inc.
Absence of promoting potential of bracken fern (Pteridium aquilinum) in rat urinary bladder carcinogenesis induced by N‐butyl‐N‐(4‐hydroxybutyl)‐nitrosamine and uracil
Authors: de Oliveira Maria Luiza , Rocha Noeme Souza , Fukushima Shoji , de Camargo João Lauro 
Published: February 2006

AbstractConventional studies on bracken fern (Pteridium aquilinum; PA) carcinogenicity have used high dietary concentrations (around 30%) and long‐term exposure (up to 52–70 weeks) without consideration of the multistep character of the chemical carcinogenesis process. The present study evaluated specifically the promoting potential of 3–5% dietary crude PA in the rat urinary bladder mucosa in a 32‐week‐long initiation‐promotion assay for chemical carcinogenesis. Initiation of urothelial carcinogenesis was accomplished with N‐butyl‐N‐(4‐hydroxybutyl)‐nitrosamine (BBN). Uracil (U) was provided through the diet in order to expand the population of initiated cells. Seven groups (G) of male Wistar rats were submitted to the following treatments: G1 = BBN (n = 8); G2 = U (n = 10); G3 = BBN‐U (n = 9); G4 = BBN‐PA‐U‐PA (n = 16); G5 = PA (n = 8); G6 = BBN‐PA (n = 10); G7 = PA‐U‐PA (n = 12). At the end of the experiment rats presenting epithelial papillary or nodular hyperplasia (PNH), papillomas (PAP), or simultaneous PNH plus PAP numbered, respectively G1: 2‐0‐1; G2: 0‐0‐0; G3: 3‐0‐2; G4: 4‐3‐2; G5: 1‐0‐1; G6: 8‐0‐0; and G7: 0‐0‐0, with no significant differences in the incidence of lesions among the groups. More frequent and more severe lesions occurred in BBN‐initiated animals, predominantly in those also exposed to uracil (G3 and G4). Low‐dose crude bracken fern in the diet does not promote rat urinary bladder carcinogenesis after a 32‐week period of exposure, even when the initiated urothelial cell population has been expanded through a mechanical stimulus. © 1995 Wiley‐Liss, Inc.