bluuebunny/crossref_metadata_2025_split huggingface dataset:
N‐nitrosoheptamethyleneimine‐induced pulmonary and esophageal carcinogenesis and effects of concomitant treatment with bleomycin in rats
Authors: Yoshida Yasunori , Hasegawa Ryohei , Takaba Katsumi , Imaida Katsumi , Ito Nobuyuki 
Published: February 2006

AbstractThe combination effects of bleomycin with N‐nitrosoheptamethyleneimine (NHMI) or dihydroxy‐di‐N‐propylnitrosamine (DHPN) on pulmonary carcinogenesis were investigated. Male F344 rats were given NHMI (20 or 40 ppm) or DHPN (200 ppm) in the drinking water and intraperitoneally injected with bleomycin (1 mg/kg) once a week for 18 weeks and then killed at week 24. Many rats treated with NHMI died before the termination of the experiment due to toxicity or development of advanced esophageal carcinomas, considered to be the main cause of death. Detailed histological examination performed on rats killed at week 24 revealed no statistically significant effects of bleomycin on NHMI or DHPN induction of neoplastic lesions in the lung or esophagus, although pulmonary carcinomas were only found in two rats treated with NHMI plus bleomycin.Under the present experimental conditions, NHMI exerted stronger carcinogenic activity in the esophagus than in the lung, and no obvious modifying effects of simultaneously administered bleomycin were evident on NHMI‐ or DHPN‐induced pulmonary carcinogenesis. © 1992 Wiley‐Liss, Inc.
Transplacental genotoxicity of triethylenemelamine, benzene, and vinblastine in mice
Authors: Xing S. G. , Shi X. , Wu Z.‐L. , Chen J.‐K. , Wallace W. , Whong W.‐Z. , Ong T. 
Published: February 2006

AbstractTransplacental cytogenetic effects of triethylenemelamine (TEM), benzene, and vinblastine on maternal mice and their fetuses have been investigated using micronucleus and sister chromatid exchange (SCE) as genetic endpoints. CD‐1 mice were treated on day 14 and 15 of gestation with TEM (0.125, 0.25, and 0.5 mg/kg), benzene (439, 878, and 1,318 mg/kg), and vinblastine (0.5, 1, and 2 mg/kg) by intraperitoneal injection at 24 hr intervals, and sacrificed 40 hr after the first injection. Erythrocytic precursor cells in maternal bone marrow and fetal livers (2–4) from each pregnant mouse were used for the micronucleus and/or the SCE analyses. Significant dose‐related increases in both micronuclei and SCE were found in maternal bone marrow and fetal liver following TEM treatment. Benzene at the highest dose (1,318 mg/kg) also caused a significant increase in micronuclei and SCE in both maternal bone marrow and fetal liver cells. The embryonic genotoxic effect of TEM was much higher than that of benzene for both genetic endpoints, and the frequency of micronuclei induced by benzene was higher in fetal liver than in maternal bone marrow cells. Vinblastine, a spindle poison, induced micronuclei but not SCE. Micronuclei induction by vinblastine was 7 fold greater in maternal bone marrow than in fetal liver cells. All three chemicals were cytotoxic in maternal bone marrow cells, but not in fetal liver cells except for TEM, which showed a weak cytotoxicity in fetal liver cells in the micronucleus assay. These results indicate that TEM, benzene, and vinblastine are transplacental genotoxicants in mice. © 1992 Wiley‐Liss, Inc.
Changes in secondary structure of DNA of rat embryos following treatment with diethylnitrosamine and methylazoxymethanol acetate in vivo
Authors: Catalano Alberto , Huang Peter H. T. 
Published: February 2006

AbstractDiethylnitrosamine (DEN) and methylazoxymethanol acetate (MAM) are not transplacental carcinogenic but embryotoxic to Wistar rats when administered by i.p. injection on day 12 of gestation. MAM, a weak teratogen to rats during this period, induced a dose dependent increase in the number of resorptions to 15% and 40% of the litters following doses of 15 and 25 mg/kg bw, respectively. Rats similarly treated with 70, 150, and 180 mg DEN/kg bw resulted in increases in total DNA mass of day 13 embryos by 31%, 45% and 52%, respectively, compared to the saline treated controls. Twenty percent reduction in total DNA amount was detected following 25 mg MAM/kg bw.Benzoylated DEAE‐cellulose (BD‐cellulose) chromatography fractionates DNA on the basis of secondary structure by stepwise elution of double‐stranded DNA with 1.0M NaCl solution (SE‐DNA) followed by elution of DNA containing single‐stranded regions with caffeine solution (CE‐DNA). Day 13 embryonic DNA was monitored by in vivo labelling with [methyl‐3H]‐thymidine (3H‐TdR) on days 6 and 7 of gestation. Significant increases in percentages of caffeine‐eluted DNA (%CE‐DNA) compared to control values were detected 24 h after treatment of day 12 embryos with 70, 150, and 180 mg DEN/kg bw. Such increases were not observed after MAM.Incorporation of [methyl‐14C]‐thymidine (14C‐TdR) into eymbryonic DNA demonstrated the effects of treatment with these compounds on DNA synthesis in vivo. When compared to saline controls, DEN induced significant increases in 14C‐TdR incorporation into embryo DNA, 1 h prior to analysis, but the increases were not proportional to the doses administered. Similar analysis of MAM treated samples showed no significant changes to %CE‐DNA values. The relative %CE‐DNA is expressed as the ratio of the percentage of caffeine‐eluted 14C‐labelled DNA to %CE‐DNA (i.e., %CE‐14C‐DNA:%CE‐3H‐DNA). In the majority of control embryos the 14C‐specific activity of CE‐DNA was higher than the 14C‐specific activity of SE‐DNA. No significant change to relative %CE‐DNA values of embryos to those of the controls was observed 24 h after treatment of day 12 gestation rats with single doses of DEN and MAM.The results of this study support the hypothesis that initiation mechanisms of teratogenesis and transplacental carcinogenesis are different. The pertinence of %CE‐DNA and realative %CE‐DNA values to teratogenesis and transplacental carcinogenesis is also discussed. © 1992 Wiley‐Liss, Inc.
Valproic acid induced abnormal development of the central nervous system of three species of amphibians: Implications for neural tube defects and alternative experimental systems
Authors: Oberemm A. , Kirschbaum F. 
Published: February 2006

AbstractEmbryos of Ambystoma mexicanum, Xenopus laevis, and Hyperolius viridiflavus taeniatus were exposed to various concentrations of valproic acid (VPA: 0.1, 1, 5, 10 mM) from blastula stage (S) 9 on up to advanced gastrulation of control embryos (S 11 1/2–12). At 10 and 5 mM VPA early development was affected in all species tested. However, the most pronounced effects occurred in Ambystoma: the neural folds appeared delayed and showed a flattened and wavy shape; the neural tube was not formed and embryos successively died. In Xenopus and Hyperolius (10, 5 mM VPA) the beginning of gastrulation was delayed up to neurulation of control embryos. In Xenopus many of the embryos completed neurulation, whereas some embryos exposed to 10 mM VPA showed neural tube defects (NTDs) of different type and degree (open neural tube at different regions of the dorsum). In Hyperolius neural folds arose around the blastoporus and fused later on (earlier in embryos treated with 5 mM VPA), but the shape of these embryos was abnormal and the development was not continued (pronounced effect at 10 mM VPA). Comparing the three species, Xenopus proved to be the least sensitive species (at 5 mM VPA 14.2% NTDs of total malformations compared to 100% in the other species). The most sensitive species, Ambystoma, developed head‐oedema at 1 mM VPA, whereas the anurans were not affected. Our results suggest a similar mechanism of VPA‐induced NTDs in mammals and amphibians. © 1992 Wiley‐Liss, Inc.
Effect of acyl derivatives of 4,4,4‐trifluoro‐1‐phenyl‐1,3‐butanedione on 2‐acetylaminofluorene‐induced glutathione S‐transferase positive foci in the rat liver
Authors: Hasegawa Ryohei , Wang Ching Y. , Kim Dae‐Joong , Lee Mei‐Sie , Yoshida Yasunori , Ito Nobuyuki 
Published: February 2006

AbstractAcyl derivatives of 4,4,4‐trifluoro‐1‐phenyl‐1,3‐butanedione (TFPB), 1‐benzoyl‐2‐tri‐fluoromethyl‐2‐acetoxyethene (BTAE), and 1‐benzoyl‐2‐trifluoromethyl‐2‐(4‐methyl‐thio)benzoyloxyethene (BTME), were synthesized and investigated for inhibition of tRNA binding by N‐acethoxy‐2‐acetylaminofluorene (N‐AcO‐AAF), and induction of glutathione S‐transferase placental form (GST‐P) positive foci in the rat liver by 2‐acetylaminofluorene (2‐AAF). Male F344 rats were given BTAE or BTME intraperitoneally and 2‐AAF by intragastric intubation. Two weeks following the treatment, the rats were maintained on the diet containing 0.05% phenobalbital for an additional 6 weeks and then killed. Development of GST‐P positive foci was not affected by concomitant treatment with BTAE or BTME. These two compounds inhibited the in vitro binding of N‐AcO‐AAF to tRNA. Thus, although these diacylmethane derivatives had the in vitro inhibitory activity, they did not inhibit tumor‐initiating activity of 2‐AAF in the rat liver. © 1992 Wiley‐Liss, Inc.
Stage‐specific effects of teratogens on sea urchin embryogenesis
Authors: Graillet C. , Pagano G. , Girard J.‐P. 
Published: February 2006

AbstractThe effect of direct (chlorambucil and allopurinol) and indirect (cyclophosphamide) teratogens on the fertilization and early development of sea urchin embryos has been investigated. Fertilization was affected by none of the drugs tested. Continuous exposure of embryos to chlorambucil (10−6 to 3 × 10−4 M) starting after fertilization delayed the first cleavage and hatching. Developmental defects in chlorambucil‐treated embryos consisted mainly of blastula and gastrula‐arrested embryos and in a limited number (25%) of plutei with malformed gut or skeleton. Post‐hatching exposure to chlorambucil led to malformed plutei only. Early (pre‐hatching) exposure to allopurinol (10−6 to 10−3 M) did not affect cleavage but induced developmental defects in a ratio comparable to chlorambucil. Post‐hatching exposure to allopurinol failed to affect the embryogenesis. The indirect teratogen cyclophosphamide (10−6 to 3 × 10−5 M) had no effect on the early embryogenesis. Results were discussed in view of using sea urchin embryos to detect and analyze the early mechanisms of teratogenic action. ©1993 Wiley‐Liss, Inc.
Mammary gland morphology and responsiveness to regulatory molecules following prenatal exposure to diethylstilbestrol
Authors: Vassilacopoulou Dido , Boylan Elizabeth S. 
Published: February 2006

AbstractFemale ACI rats were exposed to diethylstilbestrol (DES) in utero to evaluate the effects on the peri‐pubertal mammary gland with respect to 1) mammary gland morphology, 2) sensitivity to natural and synthetic estrogens, and 3) sensitivity to endogenous epidermal growth factor (EGF). Pregnant rats were injected with vehicle (sesame oil) or DES (total dose, 8.0 μg) on days 15 and 18 of gestation. DES‐exposed and control offspring were ovariectomized at 34 days of age and sacrificed at day 53 to ascertain the morphology of the mammary glands in peri‐pubertal rats. Elvax pellets containing 5 or 11 ng 17 β‐estradiol (E2) or DES were implanted subcutaneously adjacent to the third mammary gland pair. Furthermore, additional groups of rats were subjected to bilateral sialoadenectomy at the day of ovariectomy to remove the major source of endogenous EGF. A significant proportion of mammary glands of DES‐exposed animals exhibited atypical mammary gland morphology, with approximately 25% displaying hypo‐differentiation, and about 5% with aberrant hyper‐proliferation. From the pellet implantation experiments, the DES‐exposed glands were found to be refractory to stimulation by 5 and 11 ng DES; however, there was no significant difference in the degree of local stimulation elicited by either dose of E2. Sialoadenectomy at d34 had no apparent effect on mammary gland morphology in either the DES‐exposed or vehicle‐exposed groups. These data support the premise that the mammary gland of the peri‐pubertal ACI rat is morphologically and physiologically aberrant as a function of transplacental exposure to DES, with a significant percentage hypo‐differentiated and refractory to subsequent hormonal stimulation. ©1993 Wiley‐Liss, Inc.
Lack of promotion of N‐butyl‐N‐(4‐hydroxybutyl)nitrosamine‐initiated urinary bladder carcinogenesis in mice by rat cancer promoters
Authors: Tamano Seiko , Asakawa Emiko , Boomyaphiphat Pleumjit , Masui Tsuneo , Fukushima Shoji 
Published: February 2006

AbstractThe effects of dietary exposure to sodium L‐ascorbate (Na‐AsA), butylated hydroxyanisole (BHA), and diphenyl on the development of urinary bladder tumors in a mouse two‐stage carcinogenesis model were examined. Male B6C3F1 mice received 0.05% N‐butyl‐N‐(4‐hydroxybutyl) nitrosamine (BBN) in the drinking water for 4 weeks and were then treated with 5% Na‐AsA, 1% BHA, or 1% diphenyl for 32 weeks. None of these chemicals enhanced the development of either preneoplastic or neoplastic lesions in the urinary bladder. Furthermore, DNA synthesis levels of urinary bladder epithelium in mice treated with each substance alone for 8 weeks were not elevated significantly, although Na‐AsA was associated with a significant increase in the urinary pH value and Na+ concentration. The results indicate that Na‐AsA, BHA, and diphenyl do not exert an enhancing influence on mouse bladder carcinogenesis, in clear contrast to the case in the rat. ©1993 Wiley‐Liss, Inc.
Modification of hepato‐ and renal carcinogenesis by catechol and its isomers in rats pretreated with N‐ethyl‐N‐hydroxyethylnitrosamine
Authors: Okazaki Shuzo , Hoshiya Toru , Takahashi Satoru , Futakuchi Mitsuru , Saito Koichi , Hirose Masao 
Published: February 2006

AbstractModifying effects of catechol, resorcinol, and hydroquinone on second stage hepato‐ and renal carcinogenesis was investigated in rats pretreated with N‐ethyl‐N‐hydroxyethyl‐nitrosamine (EHEN).Groups of twenty 6‐week‐old Wistar/Crj male rats were treated with 0.1% EHEN in the drinking water for 3 weeks. Starting 1 week after the termination of EHEN treatment, they were given a diet containing 0.8% catechol, 0.8% resorcinol, or 0.8% hydroquinone or basal diet for 36 weeks. Further groups of 15 rats were each treated with the same doses of phenolic compounds or basal diet alone without EHEN pretreatment. All surviving animals were killed at the end of week 40 when histopathological assessment revealed significant reduction of the numbers per rat of hepatocellular adenomas and hepatocellular carcinomas by resorcinol, whereas hydroquinone significantly enhanced the numbers per rat of renal microadenomas and renal cell tumors. On the other hand, the number of α2u‐globulin positive tubules in the animals treated with hydroquinone was significantly lower than controls, without any alteration in bromodeoxyuridine (BrdU) incorporation. Lipid peroxidation, as evaluated by thiobarbituric acid reactive substance (TBARS), was at control levels in the kidneys of rats treated with hydroquinone throughout the experiment.The results showed that the known renal carcinogen hydroquinone potently enhances the second stage of EHEN‐induced renal carcinogenesis, while its isomer resorcinol inhibited hepatocarcinogenesis. α2u‐Globulin and lipid peroxidation may not play roles in hydroquinone‐associated promotion of renal carcinogenesis. ©1993 Wiley‐Liss, Inc.
Modifying influence of prior treatment with toxic agents on induction of preneoplastic and neoplastic lesions in a medium‐term multi‐organ carcinogenesis bioassay
Authors: Hagiwara A. , Tiwawech D. , Imaida K. , Tamano S. , Shibata M.‐A. , Fukushima S. , Ito N. 
Published: February 2006

AbstractThe modifying potential of prior administration of toxic agents was investigated in our multi‐organ carcinogenesis model using male F344/DuCrj rats with the aim of assessing the link between tissue damage and initiation. Animals were administered one of four toxic agents for 8 wk, and then treated with N‐diethylnitrosamine (DEN, 100 mg/kg body weight (b.w.), intraperitoneally (i.p.), single injection), N‐methylnitrosourea(MNU, 20 mg/kg b.w., i.p., four times during wk 9 and 10), and dihydroxy‐di‐N‐propylnitrosamine (DHPN, 0.1% in drinking water, during wk 11 and 12) for multi‐organ carcinogenesis. All surviving rats were killed at the end of wk 36, and the major organs carefully examined for preneoplastic and neoplastic lesion development. Immunohistochemical demonstration of glutathione S‐transferase placental form (GST‐P) positive foci was also performed to facilitate quantitative assessment of liver lesion development. D‐galactosamine (300 mg/kg b.w., i.p., once a week), a hepatotoxin, significantly inhibited the induction of GST‐P positive foci, while 4,4′‐diaminodiphenylmethane (DDPM, 0.1 % in diet), a bile duct proliferator which is itself a hepatocarcinogen, possessed enhancing activity. DDPM, also a goitrogen, clearly inhibited the development of follicular cell tumors in the thyroid. Uracil (3.0% in diet), which is an inducer of papillomatosis in the urinary bladder, did not exert any enhancing potential on bladder carcinogenesis. Bleomycin (2 mg/kg b.w., i.p., twice a week), which is an alveolar epithelium injuring agent, also did not modify the induction of alveolar epithelium proliferative lesions. These results indicate that prior organ injury by toxic agents does not always act to enhance sensitivity to carcinogenesis. ©1993 Wiley‐Liss, Inc.
Clastogenic effects of the dithiocarbamate fungicides thiram and ziram in Chinese hamster cell lines cultured in vitro
Authors: Mosesso P. , Turchi G. , Cinelli S. , Di Chiara D. , Fiore M. , Palitti F. 
Published: February 2006

AbstractWe report here the results obtained using the dithiocarbamate fungicides thiram and ziram to investigate the induction of chromosomal aberrations (CAs) in Chinese hamster ovary (CHO) cells both in the absence and presence of S9 metabolism, and in a Chinese hamster epithelial liver (CHEL) cells which retain metabolic competence to activate different classes of promutagens/procarcinogens. Both thiram and ziram proved to be strong chromosome breaking agents in the CHEL cells and CHO cells in the presence of S9 metabolism. These findings suggest that thiram and ziram require metabolic conversion to become genetically active, and corroborate the evidence that CHEL cells are suitable to activate and detect a broad spectrum of chemical procarcinogens including these two pesticides. © 1994 Wiley‐Liss, Inc.
Effect of phenacetin pretreatment on renal pelvic carcinogenesis by N‐butyl‐N‐(4‐hydroxybutyl)nitrosamine in NON/Shi mice of both sexes
Authors: Murai Takashi , Mori Satoru , Hosono Motoko , Takeuchi Yasuyoshi , Oohara Tadao , Makino Susumu , Takeda Reiji , Fukushima Shoji 
Published: February 2006

AbstractInfluences of phenacetin (PH) pretreatment on renal pelvic carcinogenesis induced by N‐butyl‐N‐(4‐hydroxybutyl)nitrosamine (BBN) were examined in NON/Shi mice of both sexes. Histopathological examination revealed that PH pretreatment enhanced not only the induction of urinary tract carcinoma but also distant metastasis of renal pelvic carcinoma by BBN in male mice. The high incidence of urinary tract carcinoma by PH pretreatment might be due to hydronephrosis and epithelial proliferative lesions enhanced by PH, since a single treatment of PH induced hydronephrosis in all mice and simple hyperplasia in 70–80% of mice used. © 1994 Wiley‐Liss, Inc.
Profile of procarbazine‐induced embryotoxicity in an embryo hepatocyte Co‐culture system and after in utero glutathione depletion
Authors: Ebron‐McCoy Marian T. , Nichols Harriette P. , Andrews James E. , Kavlock Robert J. 
Published: February 2006

AbstractProcarbazine (PCZ) is an antineoplastic agent useful in the treatment of Hodgkin's disease, brain tumors, and chronic leukemia. PCZ is dysmorphogenic to developing embryos exposed in vivo or cultured in the serum of PCZ‐treated rats. However, embryos directly cultured with PCZ (up to 400 μg/ml) or PCZ plus S‐9 liver fractions are unaffected. Since intact liver cells provide several advantages over hepatic subcellular fractions for in vitro bioactivation, we exposed rat embryos to PCZ in an embryo/hepatocyte co‐culture system. Gestation day (GD) 9.5 rat embryos exposed to 0, 200, 300, or 400 μg PCZ/ml in the presence of untreated or phenobarbital induced male rat hepatocytes failed to display toxicity. However, in a companion study GD 9.5 rat embryos cultured in the serum from PCZ‐treated rats exhibited developmental deficiencies. Studies have shown that the formation of toxic metabolites can result from glutathione (GSH) conjugation of toxicants in the liver. Therefore, in a second set of experiments, rat embryos were cultured in serum from rats pretreated with two GSH depleters (phorone and buthionine sulfoximine) and subsequently dosed with PCZ. Effects on development were enhanced when embryos were cultured in the serum from PCZ‐treated/GSH depleted rats. These data indicate that PCZ requires in vivo activation to be dysmorphogenic and further suggest that the metabolite(s) responsible for procarbazine embryotoxicity are formed readily under conditions of low GSH levels. This argues against a glutathione conjugate as the ultimate toxicant. © 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.
In vitro transforming effect of the fungicides metalaxyl and zineb
Authors: Perocco Paolo , Colacci Annamaria , Bonora Bruna , Grilli Sandro 
Published: February 2006

AbstractThe cytotoxic effects and the transforming properties of two fungicides, metalaxyl and zineb, whose mutagenic or carcinogenic activity has not been clarified yet, were analyzed in the in vitro BALB/c 3T3 cell transformation test both in the presence and in the absence of an exogenous metabolizing system. Zineb was completely detoxified when the exogenous metabolizing system was added to the target cells to increase their inherent metabolic capacity. Metalaxyl induced cell transformation at any assayed dosage, i.e., 500, 250, and 50 μg/ml, in the presence of bioactivation, and at the highest dosage (500 μg/ml) in the absence of bioactivation. The transforming effect was detectable only in the level‐II transformation cultures and it was likely linked to the induction of additional cell proliferation which allowed obtaining the transformation amplification in these experimental conditions. © 1995 Wiley‐Liss, Inc.
Evaluation of cytogenetic effects of a naturally occurring non‐ice‐nucleation Pseudomonas fluorescens strain in Chinese hamster ovary (CHO) cells
Authors: Caruso P. , Andreozzi L. , Motta S. , Mosesso P. 
Published: February 2006

AbstractOne of the main methods for eliminating ice‐nucleation‐active (INA+) bacteria, the micro‐organisms responsible for frost injuries to plants at mild freezing temperatures, is the use, as competitors, of other naturally occurring non‐nucleating strains (non‐INA). In the present article we investigated the cytogenetic effects of a naturally occurring non‐INA strain of Pseudomonas fluorescens (MS 1640 R3), evaluating the induction of chromosomal aberrations and sister chromatid exchanges (SCEs) in Chinese hamster ovary (CHO) cells in the absence and presence of rat S9 metabolism. The results obtained did not show any increase in either chromosomal aberrations or SCEs, both in the absence and presence of rat S9 metabolism when used as (i) intact bacteria cells, (ii) sonicated bacteria (i.e., potential endotoxins), or (iii) metabolic bacterial products (i.e., potential exotoxins) released in the growth medium. © 1995 Wiley‐Liss, Inc.