bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cytogenetic analysis of peripheral blood lymphocytes in workers occupationally exposed to polychlorinated biphenyls
Authors: Kalina Ivan , Šrám Radim J. , Konečná Helena , Ondruššeková Anna 
Published: February 2006

AbstractThe ability of polychlorinated biphenyls (PCBs) to induce chromosome aberrations and sister chromatid exchanges (SCE) in peripheral lymphocytes was studied in a group of workers occupationally exposed to PCBs during the production of the Czechoslovak PCB products Delor 103 and Delor 106. The effect of PCB exposure was compared between an exposed group (N = 32, 3.25 ± 0.34% aberrant cells, AB.C.), control group 1(N = 20, 1.30 ± 0.29% AB.C.), and control group 2 (N = 20, 1.60 ± 0.31% AB.C.). The length of PCB exposure over 10 yr increased the frequency of AB.C. in a group exposed for 11–15 yr to 3.40% (N = 5) and in a group exposed for 16–25 yr to 5.85% (N = 7) vs. an increase of 1.60% AB.C. in group C2 and of SCE to 12.6 ± 0.9/cell vs. 6.9 ± 0.7 SCE/cell in C2. The clastogenic activity observed in this group may be the result of a high PCB concentration in blood plasma (320 ± 190 μg PCB/1), and it is probably related to its solubility in adipose tissue, when it may act as another mutagen and carcinogen biotransformation inducer.
Quantitation and immunohistochemical localization of DNA adducts in rat embryos and associated yolk sac membranes exposed in vitro to N‐acetoxy‐2‐acetylaminofluorene (N‐Ac‐AAF)
Authors: Mirkes Philip E. , Little Sally A. , Beland Frederick A. , Huitfeldt Henrik S. , Poirier Miriam C. 
Published: February 2006

AbstractSpecific antibodies and radioimmunoassay (RIA) were used to measure the levels of acetylated and deacetylated C‐8 substituted deoxyguanosine adducts in day 11 rat embryos and their associated yolk sacs after exposure of whole rat conceptuses in vitro to the teratogen N‐acetoxy‐2‐acetylaminofluorene (N‐Ac‐AAF). The deacetylated adduct predominates in both the embryo and the associated yolk sac, and a dose response for adduct formation was observed when adducts were quantitated by RIA. Immunohistochemical localization of the deacetylated adducts revealed that adducts were confined to the nuclei in all tissues examined and that the abundance of adducts varied within and between tissues. Our initial findings indicate that specific DNA adduct antibodies may be useful in the study of teratogenesis induced by a wide variety of agents that modify DNA.
DNA strand breaks induced in cultured human and rodent cells by chlorohydroxyfuranones—mutagens isolated from drinking water
Authors: Chang Lina W. , Daniel F. Bernard , Deangelo Anthony B. 
Published: February 2006

AbstractChlorohydroxyfuranones, by‐products of chlorine disinfection and drinking water contaminants, are shown to produce DNA strand breaks in human and rodent cells. One chlorohydroxyfuranone, 3‐chloro‐4‐dichloromethyl‐5‐hydroxy‐2[5H]‐furanone (MX), a potent bacterial mutagen, induces 232 ± 89 DNA strand breaks.(cell‐μM)−1 in human CCRF‐CEM cells over a concentration range of 4.4 to 220 μM. This constitutes a DNA damage potency comparable to dimethylsulfate (DMS). By comparison, 3,4‐dichloro‐5‐hydroxy‐2[5H]‐furanone (MA), another chlorohydroxyfuranone which is approximately four orders of magnitude less mutagenic than MX in Salmonella typhimurium strain TA100 is only about tenfold less potent as an inducer of DNA strand breaks in these cells, i.e., 18.2 ± 3.1 strand breaks·(cell‐μM)±1. The DNA strand‐breaking potential of MX is inactivated by prior incubation with a rat liver S9 homogenate. In addition, both chlorohydroxyfuranones are ineffective at producing DNA strand breaks in primary rate hepatocytes (PRH) at concentrations below those which produce cytotoxicity as assessed by release of the cellular enzyme lactate dehydrogenase (LDH). Prior treatment of the PRH with μM diethyl maleate, a glutathione‐depleting agent, did not enhance the cytotoxicity nor the DNA strand‐breaking potential of either chlorohydroxyfuranone. This could indicate that glutathione‐glutathione‐S‐transferase is not an important mechanism for the detoxification of these compounds in PRH.
Heat shock proteins in human and mouse embryonic cells after exposure to heat shock or teratogenic agents
Authors: Honda Ken‐Ichi , Hatayama Takumi , Takahashi Ken‐Ichi , Yukioka Munehiko 
Published: February 2006

AbstractIn human chorionic villus tissue at the 10–17th week of a normal pregnancy, heat shock proteins (hsp70, hsp73, hsp85, and hsp105) were induced in vitro by a heat shock or by exposure to sodium arsenite or cadmium chloride. In dispersed cells of the whole mouse embryo on the 11th day of development, heat shock proteins (hsp73 and hsp105) were induced by a heat shock or by exposure to sodium arsenite, but not by exposure to cadmium chloride. After a maternal hyperthermia or an intraperitoneal injection of sodium arsenite or cadmium chloride into a pregnant mouse, heat shock proteins accumulated in the embryo on the 9th day of development, especially in the neuroepithelial tissue. The significance of heat shock proteins in the embryo is discussed. © 1992 Wiley‐Liss, Inc.
Dose response study of N‐nitrosodiethanolamine initiation of rat hepatocarcinogenesis
Authors: Ogawa Kumiko , Hasegawa Ryohei , Wada Shigetsugu , Yamaguchi Shuji , Ito Nobuyuki 
Published: February 2006

AbstractInitiating activity of N‐nitrosodiethanolamine (NDELA) for rat liver carcinogenesis was investigated using an 8‐weeks bioassay system. Male F344 rats were initially treated with a single intraperitoneal injection of NDELA at one of five dose levels: 1,600, 800, 400, 200, or 100 mg/kg. Two weeks later, the rats were placed on 0.02% 2‐acetylaminofluorene (2‐AAF) or 0.05% phenobarbital (PB) containing diet for 6 weeks. All animals were subjected to 2/3 partial hepatectomy 4 weeks after the NDELA treatment, and killed at the end of the eighth week. NDELA itself exerted low toxicity in terms of body weight gain. Clear dose‐dependent initiating activity of NDELA was observed in terms of development of glutathione S‐transferase placental form (GST‐P) positive liver cell foci, this being more apparent with PB promotion than with 2‐AAF where the enhancing regimen itself caused multiple lesion development. Initiating potential of NDELA, however, was much lower than that observed for diethylnitrosamine in our previous work. © 1992 Wiley‐Liss, Inc.
Hyperploid cells in the limb buds of rats and 5‐azacytidine‐induced digital deformities
Authors: Kurishita Akihiro , Ihara Toshio 
Published: February 2006

AbstractTo clarify the mechanism underlying the digital teratogenesis of 5‐azacytidine (5‐AC), the DNA contents of mesenchymal cells were examined in the limb buds of the rat by microspectrophotometry. 5‐AC induced hyperploid cells: 2.4% at 18 h after injection and 3.2% at 24 h. No hyperploid cells were noted 30 h after the treatment. Because posttreatment caffeine suppressed 5‐AC‐induced digital defects, the actions of caffeine on 5‐AC‐induced hyperploid cells were further studied; no hyperploid cells were detected at any sampling point. Caffeine suppressed hyperploid cells as well as digital defects. These results suggest that the causative factors of digital defects by 5‐AC may involve hyperploid cells. However, in that there were too few hyperploid cells to cause the defects, further studies are required to clarify the nature of the action of 5‐AC. © 1992 Wiley‐Liss, Inc.
Ontogeny of peroxidase activity in epithelium and eosinophils of the mouse uterus
Authors: Newbold Retha R. , Jellinck Peter H. , Metzler Manfred , McLachlan John A. 
Published: February 2006

AbstractOutbred CD‐1 mice treated for 1 or 4 days with 1 mg/kg of diethylstilbestrol (DES) at various ages after birth were examined for histochemical localization of peroxidase in the uterine epithelium. Peroxidase activity in uterine extracts was also measured by a radiometric assay and the conversion of [3H]DES to [3H]Z,Z‐dienestrol (Z,Z‐DIES). While no peroxidase activity was detected by a histochemical method in uterine epithelium from untreated 5‐day old mice, the enzyme was apparent in mice treated for 4 days with DES; uterine eosinophils were absent at this age. By day 9, DES‐induced staining for peroxidase in uterine epithelial cells and the number of uterine eosinophils had increased significantly. In addition, at this age, the biochemical assays for uterine peroxidase were sensitive enough to show that DES is converted to Z,Z‐DIES and that [3H]estradiol gives rise to 3H2O and water‐soluble radioactive metabolites. The peroxidase response to DES, determined by both histochemical and biochemical methods, increased with the age of the immature mice. These data indicate that the neonatal uterus, although deficient in eosinophils, demonstrates a peroxidase response to estrogen and that this response is localized primarily in the luminal epithelium. The role of this DES‐induced peroxidase activity in converting DES to activated metabolites that may cause cell damage is discussed. © 1992 Wiley‐Liss, Inc.
Transplacental exposure to tobacco smoke in human‐adduct formation in placenta and umbilical cord blood vessels
Authors: Hansen Claus , Sørensen Lene D. , Asmussen Inger , Autrup Herman 
Published: February 2006

AbstractSmokers are exposed to a large number of genotoxic compounds that react with DNA to form covalently bound carcinogen—DNA adducts after metabolic conversion to their biological active form. Using the P32‐postlabeling techniques, tobacco smoke related carcinogen—DNA adducts have been demonstrated in DNA isolated from human placenta and umbilical cord vein and artery obtained from 11 nonsmoking and 8 smoking normal healthy women and foetuses. The adduct level was significantly higher in tissues from smokers than from nonsmokers (P = 0.021), when all tissues were combined. Furthermore, the total adduct level was higher in maternal tissue than the level in fetal tissues (P = 0.030). The adduct level in umbilical cord vein DNA was significantly lower than in placenta, and marginally lower than in umbilical cord artery from the same donor. This suggests that the foetus can metabolise some of the genotoxic compounds found in tobacco smoke to DNA‐binding metabolites. The presence of DNA adducts in foetal tissues is indicative of potential genomic damage, that may result in an increased risk for the development of serious diseases, like cancer in childhood or later during the life span of the individual. © 1992 Wiley‐Liss, Inc.
Strategy of research for cancer—chemoprevention
Authors: Ito Nobuyuki , Imaida Katsumi 
Published: February 2006

AbstractIt has been reported that environmental chemicals are important factors in terms of both development and prevention of human cancer. For the latter, detection of early stages is an essential first step followed by clinical trials for surveying populations at risk. Thus a great deal of attention has been focused on these areas. However, investigations of possibilities for active prevention of cancer development itself form another major project. Chemoprevention of carcinogenesis, which means prevention of carcinogenesis by exogenous chemical compounds, has been investigated extensively in a variety of organs in animal models. Usually attention is concentrated on only one organ. However, antioxidants, such as BHA, exert very different effects on different organs, suggesting the necessity of whole body approaches to the question of chemoprevention. Furthermore, the mechanisms of chemoprevention, including the step of carcinogenesis, i.e., initiation, promotion, progression or whole carcinogenesis steps, in which exogenous compounds exert their protective effects, should be considered.A medium‐term bioassay system and a multi‐organ carcinogenesis system, which can be used for investigation of potential for cancer chemoprevention, have been developed in our laboratory. Dose dependent inhibitory effects were established for both BHA and α‐tocopherol in the medium‐term bioassay system, and inhibition of small intestinal carcinogenesis by catechins in green tea has also been investigated in our multi‐organ carcinogenesis protocol. It is extremely important for prevention of human cancer that we find new candidates for chemopreventive agents using animal studies.This paper reviews published reports on chemoprevention, taking into account effective stage, and proposes suitable experimental animal models for future investigations in this increasingly important area. © 1992 Wiley‐Liss, Inc.
Tumor formation and sister chromatid exchange induction by ethyl carbamate: Relationships among non‐pregnant murine females, gravid dams, and transplacentally exposed offspring
Authors: Neeper‐Bradley T. L. , Conner Mary K. 
Published: February 2006

AbstractSister‐chromatid exchange (SCE) induction and cell cycle kinetics alterations by ethyl carbamate in bone marrow of non‐gravid murine Swiss Webster, ICR/Jcl, and C57Bl/6J dams were evaluated, and data from non‐gravid females were compared with those previously reported for pregnant dams of the same strains. In addition, lung adenoma induction by ethyl carbamate in gravid Swiss Webster dams, their offspring, and in non‐pregnant Swiss Webster females was also determined. Relative cytogenetic and tumor responses in non‐gravid and gravid Swiss Webster females and their offspring were compared. In contrast to the increased sensitivity reported for gravid Swiss Webster dams versus ICR/Jcl and C57Bl/6J dams, SCE responses to 1.1, 2.2, or 3.3 mmol/kg of ethyl carbamate in non‐gravid females were approximately equivalent among strains. In Swiss Webster and C57Bl/6J (but not ICR/Jcl) strains, SCE responses in non‐gravid females at 2.2 and 3.3 were significantly lower than those of their pregnant counterparts. Tumor induction by 3.3 mmol/kg ethyl carbamate paralleled relative SCE induction with Swiss Webster dams, demonstrating a 5‐fold increase in the number of tumors relative to their offspring and a 4‐fold enhancement of tumor induction relative to their non‐pregnant counterparts. © 1992 Wiley‐Liss, Inc.
Effects of various bile acids and their sodium salts on development of pepsinogen‐altered pyloric glands in rats
Authors: Yoshida Yasunori , Tatematsu Masae , Takaba Katsumi , Shichino Yutaka , Ito Nobuyuki 
Published: February 2006

AbstractEffects of dietary bile acids and their sodium salts on the development of pepsinogen‐altered pyloric glands (PAPG) were examined in male WKY/N Crj rats initially given a single dose of 160 mg/kg body weight of N‐methyl‐N′‐nitro‐N‐nitrosoguanidine (MNNG) by gastric intubation. From week 3 the animals were administered basal diet containing 0.5% supplements of cholic acid (CA), deoxycholic acid (DCA), chenodeoxycholic acid (CDCA) or their sodium salts (Na‐C, Na‐DC and Na‐CDC), or 5% ascorbic acid (ASA) or its salt (Na‐AS) for 18 weeks. The concentration of DCA and Na‐DC was reduced to 0.3% from week 12. At week 20, animals were killed and the numbers of immunohistochemically‐demonstrated PAPG were determined. Values were significantly higher with Na‐C and Na‐CDC than with the corresponding parent acids, and in the Na‐C case PAPG development was greater than with MNNG alone. In addition, Na‐CDC itself induced the numbers of PAPG significantly. These results suggest that bile salts are possible intrinsic promoters of gastric carcinogenesis. They were without effect, however, on forestomach lesions. © 1992 Wiley‐Liss, Inc.
The modulatory effects of tryptamine and tyramine on the S9‐mediated mutagenesis of IQ and MelQ in Salmonella strain TA98
Authors: Abu‐Shakra Amal 
Published: February 2006

AbstractThe S9‐mediated mutagenesis of IQ and MeIQ in Salmonella strain TA98 was modulated by introduction to the assay of tryptamine or tyramine. Both biogenic amines inhibited or enhanced the mutagenic response as a function of amine concentration, strain of rat used as the S9 source, and the IQ‐type mutagen tested. Enhancement of IQ mutagenesis by tryptamine (10–80 μM) was observed in the presence of S9 preparations derived from Aroclor 1254‐pretreated Fischer rats; the enhancing effect ceased at tryptamine concentrations > 160 μM. When Sprague‐Dawley‐S9 or Wistar‐S9 were used for activation, the enhancement of IQ mutagenesis by tryptamine shifted to inhibition at tryptamine concentrations >40 μM, with Sprague‐Dawley‐S9, and > 20μM, with Wistar‐S9. By contrast, MeIQ‐mutagenesis was enhanced by tryptamine (10 – 160μM), regardless of the rat strain used as S9 source. Tyramine was a weaker enhancer of MeIQ mutagenesis than was tryptamine and, unlike tryptamine, its inhibitory effects on IQ mutagenesis were observed only with Wistar‐S9. Tryptamine (10–80 μM) inhibited cytochromes P450IA1 and P450IA2 activities, monitored by the O‐deethylation of ethoxyresorufin and Glu‐P‐1 mutagenesis in TA98, respectively. These data suggest that the effects of biogenic amines on IQ and MeIQ bioactivation are complex. Furthermore, this study demonstrates that tryptamine and tyramine act both as enhancers (comutagens) and as inhibitors (antimutagens) of IQ and MeIQ mutagenesis, depending on the testing conditions. © 1992 Wiley‐Liss, Inc.
Methotrexate increases valproic acid‐induced developmental toxicity, in particular neural tube defects in mice
Authors: Elmazar M. M. A. , Nau H. 
Published: February 2006

AbstractThe hypothesis that valproic acid‐induced dysmorphogenesis may be due to an interference of this drug with folate metabolic pathways was further investigated by a study of a possible interaction of valproic acid (VPA) and the established folate antagonist methotrexate (MTX). The dihydrofolate reductase inhibitor MTX (1.25 and 2.5 mg/kg, i. p.) was injected 15 min prior to VPA (300 and 400 mg/kg, s. c.) in day 8 pregnant NMRI mice. Fetuses were examined for exencephaly, resorption, and fetal weight retardation on day 18 of gestation. MTX produced no exencephaly or reduction in fetal weight, and the 2.5‐mg/kg dose caused 56% resorption. Higher doses (5–20 mg/kg) produced embryolethality and fetal weight retardation, but no exencephaly. VPA (300 and 400 mg/kg) administration resulted in 3.4% and 12.6% exencephaly and 9% and 19% resorptions, respectively. Coadministration of MTX with VPA significantly increased VPA‐induced resorption and exencephaly rates as well as fetal weight retardation. Exencephaly induced by VPA 400 mg/kg was increased to 29.5% and 24.1% (P < 0.01 and P < 0.05) when given with 1.25 and 2.5 mg/kg MTX, respectively. MTX (2.5 mg/kg i.p.) did not alter transplacental VPA (400 mg/kg, s.c.) pharmacokinetics. These results support the view that VPA‐induced teratogenesis may be mediated by interaction with folate metabolism. © 1992 Wiley‐Liss, Inc.
Teratological study of stobadin after single and repeated administration in rats
Authors: Ujházy Eduard , Balonová Tatiana , Vargová Tamara , Janšák Jozef , Derková L'Ubica 
Published: February 2006

AbstractThe toxic developmental potential of the anti‐arrhythmic drug stobadin was assessed after single intravenous or repeated oral doses to pregnant rats. Stobadin was studied in the form of dihydrochloride (DH 1011) at doses of 2 and 6 mg/kg, given in single intravenous injections on days 3,6,9, or 12 of gestation. Immediately after injection of the 6‐mg/kg dose of DH 1011 to pregnant rats, saccade abdominal respiration, tremor of hindlimbs, and sedative behaviour were observed on each day of medication. No deaths of females occurred in either the control or experimental groups. Slight foetal toxicity was manifested by significantly decreased foetal weight only after treatment on day 3 of gestation at 6 mg/kg and by significantly increased incidence of delayed ossification of the parietal and supraoccipital bone also at 6 mg/kg DH 1011 given on day 12 of gestation. The effect of repeated oral treatment in the form of dipalmitate salt (DP 1031) was studied in doses of 5, 15, and 45 mg/kg from days 2–15 of gestation. Oral exposure to 45 mg/kg DP 1031 resulted in significant reduction of maternal body weight gain and in embryofoetal toxicity, namely, increased preimplantation foetal loss, anomalies of sternebrae, and, after 15 and 45 mg/kg DP 1031, significantly decreased foetal weight and smaller litter size. The relevance of the two routes of stobadin administration for risk extrapolation is discussed. © 1992 Wiley‐Liss, Inc.
Analysis of cytogenetic damage induced in CHO cells by the pyrethroid insecticide fenvalerate
Authors: Caballo Covadonga , Herrera Angustias , Barrueco Carmen , Santa‐María Ana , Sanz Félix , de la Peña Eduardo 
Published: February 2006

AbstractA synthetic pyrethroid insecticide, fenvalerate, was tested for its ability to induce chromosome aberrations (CA) and sister chromatid exchanges (SCE) in CHO cells. Fenvalerate was assayed both in the presence and in the absence of a rat liver activation system (S9‐mix).Our results indicate that fenvalerate in the presence of S9‐mix is able significantly to increase the frequency of CA, while in the SCE test this increase occurred both in the presence and in the absence of S9‐mix.In addition, fenvalerate affected the cell cycle, causing a decrease in the mitotic index (MI) and in the proliferative rate index (PRI). © 1992 Wiley‐Liss, Inc.
Analysis of carcinogenic activity of some pesticides in a medium‐term liver bioassay in the rat
Authors: Hakoi K. , Cabral R. , Hoshiya T. , Hasegawa R. , Shirai T. , Ito N. 
Published: February 2006

AbstractEight pesticides were tested in a medium‐term bioassay based upon the induction of preneoplastic lesions in the liver. Rats were initially given diethylnitrosamine intraperitoneally at a dose of 200 mg/kg body weight and 2 weeks later were treated with the pesticides for 6 weeks and then killed; all rats had a partial hepatectomy at week 3. Hepatocarcinogenic potential was assessed by comparing the number and area of glutathione S‐transferase placental form positive foci in the liver with those of controls given diethylnitrosamine (DEN) alone. Positive results were seen with p,p‐DDT and Triadimefon. Permethrin (mixture of 39% cis form and 61% trans form) showed borderline results. Permethrin (25/75), Deltamethrin, Cypermethrin (52/48), while Trimorphamide and Propineb gave negative results. Our findings provide experimental evidence to indicate that compounds active in this assay have a potential for liver carcinogenicity in rodents. © 1992 Wiley‐Liss, Inc.
Comparative joint actions of semicarbazide and thiosemicarbazide on induction of malformations and osteolathyrism in mixtures with benzoic hydrazide
Authors: Dawson Douglas A. 
Published: February 2006

AbstractA developed mixture testing protocol, evaluating malformation of Xenopus embryos, was used to examine the joint actions of semicarbazide (SC) and thiosemicarbazide (TSC) with benzoic hydrazide (BZH). These compounds were selected to evaluate the effect of a substitution of sulfur for oxygen on osteolathyrism induced in Xenopus embryos. Binary combinations of SC with BZH and TSC with BZH were tested using three mixture ratios for each combination. Each compound was simultaneously tested alone in 96 h static‐renewal tests, starting with late‐blastula stage embryos. Toxic unit analysis, evaluating induction of malformations in general and osteolathyrism specifically, indicated the joint action for each combination was concentration addition. The results indicate that the three chemicals are similar and non‐interactive and are likely to induce osteolathyrism by the same primary mechanism of action. ©1993 Wiley‐Liss, Inc.