Check out our New Publishers' Select for Free Articles

Archives of Toxicology (v.85, #9)

A user-friendly guide on how to obtain and accurately interpret information from metabolic databases by C. Cadenas; R. Marchan (pp. 1013-1014).

A survey of metabolic databases emphasizing the MetaCyc family by Peter D. Karp; Ron Caspi (pp. 1015-1033).

Thanks to the confluence of genome sequencing and bioinformatics, the number of metabolic databases has expanded from a handful in the mid-1990s to several thousand today. These databases lie within distinct families that have common ancestry and common attributes. The main families are the MetaCyc, KEGG, Reactome, Model SEED, and BiGG families. We survey these database families, as well as important individual metabolic databases, including multiple human metabolic databases. The MetaCyc family is described in particular detail. It contains well over 1,000 databases, including highly curated databases for Escherichia coli, Saccharomyces cerevisiae, Mus musculus, and Arabidopsis thaliana. These databases are available through a number of web sites that offer a range of software tools for querying and visualizing metabolic networks. These web sites also provide multiple tools for analysis of gene expression and metabolomics data, including visualization of those datasets on metabolic network diagrams and over-representation analysis of gene sets and metabolite sets.

Keywords: Metabolic databases; Bioinformatics; Metabolic pathways; Databases; Genome databases

In vivo and ex vivo percutaneous absorption of [¹⁴C]-bisphenol A in rats: a possible extrapolation to human absorption? by Fabrice Marquet; Jean-Paul Payan; Dominique Beydon; Ludivine Wathier; Marie-Christine Grandclaude; Elisabeth Ferrari (pp. 1035-1043).

Bisphenol A (BPA) is a monomer used mainly in the synthesis of polycarbonates and epoxy resins. Percutaneous absorption is the second source of exposure, after inhalation, in the work environment. However, studies on this route of absorption are lacking or incomplete. In this study, percutaneous BPA absorption was measured in vivo and ex vivo in the rat, and ex vivo in humans. An approximately 12-fold difference in permeability between rat skin and human skin was found, with permeability being higher in the rat. In addition, inter- and intra-individual variability of up to tenfold was observed in humans. No accumulation of BPA in the skin was found during exposure. The skin clearance rate following exposure was estimated at 0.4 μg/cm²/h. Ex vivo and in vivo percutaneous absorption fluxes of BPA in the rat were in the same range (about 2.0 μg/cm²/h), suggesting that extrapolation to the in vivo situation in humans may be possible. The European tolerable daily intake (TDI) of BPA is 50 μg/kg body weight. However, many research projects have highlighted the significant effects of BPA in rodents at doses lower than 10 μg/kg/day. A 1-h occupational exposure over 2,000 cm² (forearms and hands) may lead to a BPA absorption of 4 μg/kg/day. This is 8% of the European TDI and is very close to the value at which effects have been observed in animals. This absorption must therefore be taken into account when evaluating risks of BPA exposure, at least until more relevant results on the toxicity of BPA in humans are available.

Keywords: Bisphenol A; Percutaneous absorption; Rat; Human; In vivo; Ex vivo

Hepatic transcriptome and proteome responses against diethyl maleate-induced glutathione depletion in the rat by Shusuke Yamauchi; Naoki Kiyosawa; Yosuke Ando; Kyoko Watanabe; Noriyo Niino; Kazumi Ito; Takashi Yamoto; Sunao Manabe; Atsushi Sanbuissho (pp. 1045-1056).

Hepatic transcriptome and proteome responses against glutathione depletion were investigated by Affymetrix GeneChip Microarray and 2-dimensional gel electrophoresis (2D-DIGE), followed by MALDI-TOF–MS analysis and utilizing a glutathione-depleted rat model treated with diethyl maleate (DEM). Hepatic glutathione content decreased to 1.29 μmol/g liver (25.5% compared to control) after DEM treatment, and there were no apparent hepatotoxic signs estimated by blood chemistry examinations. A total of 247 and 213 annotated gene probe sets exhibited greater than twofold up- and down-regulation compared with controls, respectively. The up-regulated gene list contained a number of glutathione depletion–responsive genes reported previously, such as Trib3, Srxn1, Myc, Asns, Igfbp1, Txnrd1, or Hmox1, suggesting that these genes are robust mRNA biomarkers for evaluating hepatic glutathione depletion. In the 2D-DIGE analysis, proteins for a total of 361 spots were identified by MALDI-TOF–MS analysis. Of the identified proteins, 5 and 14 proteins showed up- and down-regulation, respectively. Some proteins exhibited differential expression in the protein level but not in the mRNA level, including L-FABP, MAWDBP, aldo–keto reductase family 1 member A1, catalase and ATP synthase subunit beta, suggesting that these proteins would be potential protein biomarkers for evaluating glutathione depletion. Moreover, up-regulation of FABP1 protein along with up-regulation of PPARα-regulated gene transcripts (i.e., Acot2 and Acot4) is indicative of PPARα activation, which may contribute to hepatocellular protection against glutathione depletion–induced oxidative stress. The up-regulation of L-FABP1 was detected by proteome data but not by transcriptome data, demonstrating the advantage of utilizing transcriptomics and proteomics combination to investigate glutathione depletion–induced molecular dynamics.

Keywords: Liver; Glutathione; Microarray; Proteomics; Toxicogenomics

Ceramide induces apoptosis via caspase-dependent and caspase-independent pathways in mesenchymal stem cells derived from human adipose tissue by Ji Yeon Park; Moon Jung Kim; Yong Keun Kim; Jae Suk Woo (pp. 1057-1065).

Apoptosis of stem cells may be related to certain degenerative conditions such as progressive tissue damage and an inability to repair. Ceramide induces cell death in various cell types. However, the underlying mechanisms of ceramide-induced cell death in stem cells are not explored. This study was designed to investigate the cell death process caused by cell-permeable ceramide and to determine the underlying mechanisms in mesenchymal stem cells derived from human adipose tissue (hASCs). Ceramide caused a loss of cell viability in a concentration- and time-dependent manner, which was largely attributable to apoptosis. Ceramide induced generation of reactive oxygen species (ROS) and disruption of the mitochondrial membrane potential. The ROS generation caused by ceramide was prevented by the antioxidant N-acetylcysteine (NAC). Although ceramide induced release of cytochrome c from mitochondria and activation of caspase-3, the ceramide-induced cell death was partially prevented by caspase inhibitors. Addition of ceramide caused apoptosis-inducing factor (AIF) nuclear translocation, which was prevented by antioxidant. Taken together, these data suggest that ceramide induces cell death through both caspase-dependent and caspase-independent mechanisms mediated by ROS generation in hASCs.

Keywords: Ceramide; Apoptosis; Reactive oxygen species; Caspase; Apoptosis-inducing factor; Mesenchymal stem cells derived from human adipose tissue

Cadmium chloride inhibits lactate gluconeogenesis in isolated human renal proximal tubules: a cellular metabolomic approach with ¹³C-NMR by Hassan Faiz; Agnès Conjard-Duplany; Michelle Boghossian; Guy Martin; Gabriel Baverel; Bernard Ferrier (pp. 1067-1077).

As part of a study on cadmium nephrotoxicity, we studied the effect of cadmium chloride (CdCl₂) in isolated human renal proximal tubules metabolizing the physiological substrate lactate. Dose–effect experiments showed that 10–500 μM CdCl₂ reduced lactate removal, glucose production and the cellular levels of ATP, coenzyme A, acetyl-coenzyme A and of reduced glutathione in a dose-dependent manner. After incubation with 5 mM l-[1-¹³C]-, or l-[2-¹³C]-, or l-[3-¹³C] lactate or 5 mM l-lactate plus 25 mM NaH¹³CO₃ as substrates, substrate utilization and product formation were measured by both enzymatic and carbon 13 NMR methods. Combination of enzymatic and NMR measurements with a mathematical model of lactate metabolism previously validated showed that 100 μM CdCl₂ caused an inhibition of flux through lactate dehydrogenase and alanine aminotransferase and through the entire gluconeogenic pathway; fluxes were diminished by 19% (lactate dehydrogenase), 28% (alanine aminotransferase), 28% (pyruvate carboxylase), 42% (phosphoenolpyruvate carboxykinase), and 52% (glucose-6-phosphatase). Such effects occurred without altering the oxidation of the lactate carbons or fluxes through enzymes of the tricarboxylic acid cycle despite a large fall of the cellular ATP level, a marker of the energy status and of the viability of the renal cells. These results that were observed at clinically relevant tissue concentrations of cadmium provide a biochemical basis for a better understanding of the cellular mechanism of cadmium-induced renal proximal tubulopathy in humans chronically exposed to cadmium.

Keywords: Nephrotoxicity; Cadmium; Metabolism; Lactate; Human; Gluconeogenesis

Oxidized low-density lipoprotein and tissue factor are involved in monocrotaline/lipopolysaccharide-induced hepatotoxicity by Mohamed A. Hammad; Mohamed Sadek Abdel-Bakky; Larry A. Walker; M. K. Ashfaq (pp. 1079-1089).

These studies were aimed at characterizing an animal model of inflammation-induced hepatotoxicity that would mimic features of idiosyncratic liver toxicity observed in humans. An attempt was made to identify oxidative damage and the involvement of coagulation system in liver after monocrotaline (MCT) administration under the modest inflammatory condition induced by lipopolysaccharide (LPS) exposure. Mice were given MCT (200 mg/kg) or an equivalent volume of sterile saline (Veh.) po followed 4 h later by ip injection of LPS (6 mg/kg) or vehicle. Mice co-treated with MCT and LPS showed increased plasma alanine aminotransferase (ALT), decrease in platelet number, and a reduction in hematocrit. Accumulation of oxidized low-density lipoprotein (ox-LDL) was remarkably higher in the liver sections of mice co-treated with MCT and LPS compared to those given MCT or LPS alone. A similar trend was observed in the expression of CXCL16 receptor in the same liver sections. Elevated expression of tissue factor (TF) and fibrinogen was also observed in the liver sections of MCT/LPS co-treated mice. The in vitro results showed that incubation of HepG2 cells with CXCL16 antibody strongly diminished uptake of ox-LDL. Expression of ox-LDL, CXCL16, and TF represents an early event in the onset of hepatotoxicity induced by MCT/LPS; thus, it may contribute to our understanding of idiosyncratic liver injury and points to potential targets for protection or intervention.

Keywords: Hepatotoxicity; Lipopolysaccharide; Monocrotaline; Pyrrolizidine alkaloids; Tissue factor; Oxidized low-density lipoprotein

Existence of a threshold for hydroxyl radical generation independent of hypoxia in rat striatum during carbon monoxide poisoning by Shuichi Hara; Hajime Mizukami; Kunihiko Kurosaki; Fumi Kuriiwa; Toshiji Mukai (pp. 1091-1099).

We examined the role of hypoxia in the carbon monoxide (CO)-induced generation of the hydroxyl radical (^•OH) in the striatum, which could contribute to brain damage due to CO poisoning. Exposure of free-moving rats to 1,000 and 3,000 ppm CO or 8 and 5% O₂ for 40 min caused concentration-dependent hypoxic conditions in terms of carboxyhemoglobin (COHb), deoxyhemoglobin, oxyhemoglobin, and O₂ contents in arterial blood. The hypoxic conditions seemed comparable between 3,000 ppm CO and 5% O₂, although alterations of pH and partial O₂ pressure (PO₂) were complex and concentration independent. In the striatum, CO and low O₂ decreased tissue PO₂ levels in a concentration-dependent and concentration-independent manner, respectively, but levels at the end of exposure were comparable among all groups. This was also the case for the increase in striatal blood flow. Although the increases in extracellular glutamate (excitatory), taurine (inhibitory), and alanine (non-neurotransmitter), in the striatum in response to CO and low O₂ were complex, 3,000 ppm CO and 5% O₂ had comparable effects. Thus, 3,000 ppm CO and 5% O₂ seemed to induce comparable hypoxic conditions. Nevertheless, the former more strongly stimulated ^•OH generation in the striatum than the latter. In addition, in contrast to low O₂ which caused a concentration-dependent increase in ^•OH, 1,000 ppm CO had no effect. The findings suggest that striatal ^•OH generation due to CO poisoning may be independent of hypoxia per se and that a threshold might exist.

Keywords: Carbon monoxide; Brain hypoxia; Rat striatum; Hydroxyl radical

Fenvalerate induces germ cell apoptosis in mouse testes through the Fas/FasL signaling pathway by Xian-Feng Zhao; Qun Wang; Yan-Li Ji; Hua Wang; Ping Liu; Cheng Zhang; Ying Zhang; De-Xiang Xu (pp. 1101-1108).

Fenvalerate has a potentially adverse effect on male reproduction and spermatogenesis, whereas the precise mechanism remains obscure. The present study investigated the effects of fenvalerate on germ cell apoptosis in testes. Adult male mice were administered with fenvalerate (15 or 60 mg/kg) by gavage for 28 days. Germ cell apoptosis was determined by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL). The number of TUNEL+ germ cells per tubule and the percentage of tubules with TUNEL+ germ cells were significantly increased in testes of mice treated with fenvalerate in a dose-dependent manner. TUNEL+ germ cells were observed mainly in stages VII–VIII and also stages IX–XII seminiferous tubules in testes. Additional experiments showed that fenvalerate increased the level of active caspase-8 and caspase-3 in testes. In addition, fenvalerate upregulated the expression of Fas and FasL in testes. No significant difference on the expression of Bcl-2 and Bax in testes was observed between fenvalerate-treated mice and controls. Fenvalerate did not affect the leakage of cytochrome c from mitochondria into cytoplasm. In addition, fenvalerate did not cause the activation of caspase-9 in testes. Taken together, these results suggest that fenvalerate induces germ cell apoptosis in testes through the Fas/FasL signaling pathway.

Keywords: Fenvalerate; Testis; Germ cells; Apoptosis; Fas/FasL pathway

Life stage-related differences in susceptibility to acrylamide-induced neural and testicular toxicity by Miwa Takahashi; Kaoru Inoue; Naoki Koyama; Midori Yoshida; Kaoru Irie; Tomomi Morikawa; Makoto Shibutani; Masamitsu Honma; Akiyoshi Nishikawa (pp. 1109-1120).

In order to assess age-dependence of susceptibility to acrylamide (ACR)-induced neural and testicular toxicity, 3- and 7-week-old male SD rats were given ACR at 0, 50, 100, or 200 ppm in the drinking water for 4 weeks, and the nervous and male reproductive systems were examined histopathologically. Testicular genotoxicity was evaluated with the comet assay and the micronucleus (MN) test. Glutathione S-transferase (GST) activity and glutathione (GSH) content in the liver and testis were also measured. In both young and adult animals, neurotoxicity was evident from 100 ppm and increased in proportion to ACR intake per body weight. In the testis, marked degeneration and exfoliation, mainly of spermatids, were observed from 100 ppm limited to young animals. The comet assay revealed ACR to significantly induce DNA damage from 100 ppm in both life stages, while MNs were found only in young rats from 100 ppm. The level of GST activity in the testis of young rats at the end of experiment was significantly lower than that of adult animals, regardless of the ACR treatment. There were no life stage-related differences in GSH contents in the liver and testis. These results suggest that susceptibility to neurotoxicity might not differ between young and adult rats when exposure levels are adjusted for body weight. Regarding testicular toxicity, young animals around puberty proved more susceptible than adult animals, possibly due to their lower level of testicular GST activity than that in adult animals.

Keywords: Acrylamide; Age; Susceptibility; Neurotoxicity; Testicular toxicity; Rat

A single intratracheal instillation of single-walled carbon nanotubes induced early lung fibrosis and subchronic tissue damage in mice by Eun-Jung Park; Jinkyu Roh; Soo-Nam Kim; Min-sung Kang; Young-Ah Han; Younghun Kim; Jin Tae Hong; Kyunghee Choi (pp. 1121-1131).

Large amounts of nanomaterials may reach both the natural and occupational environments. This represents a potential health hazard. People have forecasted that CNTs may lead to the toxicity such as mesothelioma and fibrosis like asbestos. To identify dominant immune responses induced by SWCNTs, we investigated the composition of bronchioalveolar lavage (BAL) cells, the secretion of cytokine and collagen, histopathology, protein expression, and cell phenotypes over time after a single administration of single-walled carbon nanotubes (SWCNT). In our results, the number of total cells and macrophages remained at the up-regulated level until Day 28, neutrophils rapidly increased at Day 1, and lymphocytes increased from Day 7. In the BAL fluid, pro-inflammatory cytokines rapidly increased at Day 1 and remained at an up-regulated level throughout the experimental period. IL-12 and IL-10 rapidly increased at Day 1 after administration and remained at a similar level until Day 28. IFN-γ and IL-4 reached the maximum at Day 1, and IL-5, TGF-β, and collagen reached the maximum at Day 7. IL-13 and IL-17 increased in a time-dependent manner. The distribution of B cells and cytotoxic T cells markedly increased at Days 7 and 14, and fibrotic lesions were histopathologically observed at Days 7 and 14. The expressions of caspase-3, p53, COL1A1, COX-2, iNOS, MMP-9, and MMP-2 were also markedly increased at Days 7 and 14. In addition, the expression of mesothelin, iNOS, MMP-9, and p53 was up-regulated until Day 28. Based on these findings, we suggest that a single intratracheal instillation of SWCNTs may induce early lung fibrosis and subchronic tissue damage.

Keywords: SWCNT; Lung fibrosis; Mesothelin; Cytokine; Inflammation

Shiga toxin type 2 (Stx2), a potential agent of bioterrorism, has a short distribution and a long elimination half-life, and induces kidney and thymus lesions in rats by Yue-Nan Liu; Sheng-han Wang; Tao Li; Qin Wang; Wei Tu; Kun Cai; Xiao-Jun Hou; Ren-Mao Tian; Xiang Gao; Hao Liu; Le Xiao; Jing Shi; Yuan-Guo Cheng; Jian-Chun Li; Hui Wang (pp. 1133-1140).

Shiga toxin type 2, a major virulence factor produced by the Shiga toxin–producing Escherichia coli, is a potential toxin agent of bioterrorism. In this study, iodine-125 (¹²⁵I) was used as an indicator to describe the in vivo Stx2 biodistribution profile. The rats were injected intravenously (i.v.) with ¹²⁵I-Stx2 at three doses of 5.1–127.5 μg/kg body weight. Stx2 had a short distribution half-life (t _1/2α, less than 6 min) and a long elimination half-life in rat. The toxicokinetics of Stx2 in rats was dose dependent and nonlinear. Stx2 concentrations in various tissues were detected at 5-min, 0.5-h, and 72-h postinjection. High radioactivity was found in the lungs, kidneys, nasal turbinates, and sometimes in the eyes, which has never been reported in previous studies. In a preliminary assessment, lesions were found in the kidney and thymus.

Keywords: Shiga toxin type 2; Toxicokinetics; Tissue distribution; bioterrorism

Prevention of benzene-induced genotoxicity in bone marrow and lung cells: superiority of polyphenolic acetates to polyphenols by Ajit Kumar; Anupam Sushama; Vishwajeet Rohil; Sushma Manral; Sukanya Gangopadhyay; Ashok K. Prasad; Hanumantharao G. Raj; Virender S. Parmar (pp. 1141-1150).

Previous investigations carried out in our laboratory have highlighted that 7,8-diacetoxy-4-methylcoumarin demonstrates a mechanism-based inhibition of cytochrome P450 (Cyt-P450) activities such as microsome-mediated aflatoxin B₁ (AFB₁) epoxidation, dealkylation of alkylated resorufin, and toxicokinetics of benzene. 7,8-Diacetoxy-4-methylcoumarin, quercetin pentaacetate, and ellagic acid peracetate were also found to be effective in giving the protection of AFB₁-induced genotoxicity in rat’s bone marrow and lung cells possibly due to acetylation of Cyt-P450 apoprotein mediated by acetoxy drug: protein transacetylase. Later, this transacetylase was identified as calreticulin, and the acetyltransferase function of calreticulin was appropriately termed calreticulin transacetylase. In this communication, we have focused on the superiority of several classes of polyphenolic acetates to polyphenols in the modification of Cyt-P450-linked mixed function oxidases (MFOs) such as 7-ethoxyresorufin O-deethylase (EROD) and pentoxyresorufin O-dealkylase (PROD). Special attention has also been focused on benzene-induced genotoxicity in bone marrow and lung cells. Results clearly indicated that polyphenolic acetates demonstrated time-dependent inhibition of Cyt-P450-linked MFOs, while parent polyphenols failed to demonstrate the same. Polyphenolic acetates were found to be more superior to polyphenols in preventing benzene-induced micronuclei formation. The pattern of inhibition of Cyt-P450-dependent MFOs and benzene-induced micronuclei formation by polyphenolic acetates was found in tune with their specificities to calreticulin transacetylase. These results further substantiated that inhibition of Cyt-P450-linked MFOs and benzene-induced genotoxicity in bone marrow and lung cells by polyphenolic acetates are mediated by the action of calreticulin transacetylase that catalyzes the acetylation of concerned proteins.

Keywords: Benzene; Micronuclei; Genotoxicity; Polyphenolic acetates; Calreticulin transacetylase

Protective properties of quercetin against DNA damage and oxidative stress induced by methylmercury in rats by Gustavo Rafael Mazzaron Barcelos; Denise Grotto; Juliana Mara Serpeloni; José Pedro Friedmann Angeli; Bruno Alves Rocha; Vanessa Cristina de Oliveira Souza; Juliana Tanara Vicentini; Tatiana Emanuelli; Jairo Kenupp Bastos; Lusânia Maria Greggi Antunes; Siegfried Knasmüller; Fernando Barbosa Jr (pp. 1151-1157).

Aim of the study was to find out whether consumption of quercetin (QC), an abundant flavonoid in the human diet, protects against DNA damage caused by exposure to organic mercury. Therefore, rats were treated orally with methylmercury (MeHg) and the flavonoid with doses that reflect the human exposure. The animals received MeHg (30 μg/kg/bw/day), QC (0.5–50 mg/kg/bw/day), or combinations of both over 45 days. Subsequently, the glutathione levels (GSH) and the activities of glutathione peroxidase (GPx) and catalase (CAT) were determined, and DNA damage was measured in hepatocytes and peripheral leukocytes in single cell gel electrophoresis assays. MeHg decreased the concentration of GSH and the activity of GPx by 17 and 12%, respectively and caused DNA damage to liver and blood cells, while with QC no such effects were seen. When the flavonoid was given in combination with MeHg, the intermediate and the highest concentrations (5.0 and 50.0 mg/kg/bw/day) were found to cause DNA protection; DNA migration was reduced by 54 and 65% in the hepatocytes and by 27 and 36% in the leukocytes; furthermore, the reduction in GSH and GPx levels caused by MeHg treatment was restored. In summary, our results indicate that consumption of QC-rich foods may protect Hg-exposed humans against the adverse health effects of the metal.

Keywords: Quercetin; Methylmercury; DNA damage; Antioxidant; Redox status; Comet assay

Relationship between CYP1A induction by indole-3-carbinol or flutamide and liver tumor-promoting potential in rats by Keisuke Shimamoto; Yasuaki Dewa; Sayaka Kemmochi; Eriko Taniai; Hitomi Hayashi; Masako Imaoka; Makoto Shibutani; Kunitoshi Mitsumori (pp. 1159-1166).

To investigate liver tumor-promoting potentials of indole-3-carbinol (I3C) and flutamide (FLU), changes in mRNA expression of Cyp1a and genes encoding antioxidant/detoxifying enzymes in the liver, 6-week-old male F344 rats were subjected to medium-term liver bioassay. β-Naphthoflavone (BNF), a strong CYP1A inducer, was also used for comparison. Two weeks after initiation with N-diethylnitrosamine (DEN), animals were fed a basal diet (untreated controls) or a diet containing 0.5% I3C, 0.1% FLU, or 0.5% BNF for 6 weeks. Each animal was subjected to a two-third partial hepatectomy 1 week after the start of promoter treatments. Histopathologically, I3C and BNF increased altered liver cell foci with the incidence (3.7- and 7.3-fold) and multiplicity (8.3- and 13.8-fold) compared with the DEN-alone group, respectively. Immunohistochemically, I3C significantly increased the number (3.1-fold; P < 0.01) and area (2.4-fold; P < 0.05) of foci positive for glutathione-S-transferase placental form (GST-P) compared with the DEN-alone group; FLU induced a slight but significant increase in the number of GST-P-positive foci (2.8-fold; P < 0.05) whereas BNF showed marked induction of the number and area of GST-P-positive foci (20- and 14-fold, respectively; P < 0.01). In parallel, I3C, FLU, and BNF markedly increased mRNA levels of Cyp1a1 (50-, 23-, 299-fold) and antioxidant/detoxifying enzymes such as Gpx2 and Nqo1 as shown by real-time reverse transcription-polymerase chain reaction analysis. These results suggest that I3C and FLU could promote hepatocellular tumors in parallel with that of CYP1A’s potential to cause subsequent oxidative stress responses in rats.

Keywords: CYP1A inducer; Indole-3-carbinol; Flutamide; β-Naphthoflavone; Tumor promotion; Hepatocarcinogenesis

DNA damage in fetal liver cells of turkey and chicken eggs dosed with aflatoxin B₁ by J. G. Williams; U. Deschl; G. M. Williams (pp. 1167-1172).

The present study was undertaken to investigate the potential of the potent hepatocarcinogen aflatoxin B₁ (AFB) to produce DNA damage in turkey and chicken fetal livers in ovo. Effects of a single injection of two different doses (0.062 and 6.2 μg) of AFB were examined under both short-term (4 h) and longer-term (4 day) dosing of eggs from turkeys at 24 days and chickens at 18 days of development. Liver cells prepared from the fetuses were used to assess the extent of DNA damage by the alkaline single-cell gel electrophoresis (comet) assay. The results demonstrate that AFB produces dose-related DNA damage in the fetal livers of both turkeys and chicken at 4 h, which was reduced by 4 days. Turkey embryos appeared to be slightly more susceptible to AFB damage, although no difference in the survival between chicken and turkey fetuses was observed.

Keywords: Aflatoxin B1; DNA damage; Liver; Turkey; Chicken

Sections

Personal tools

Archives of Toxicology (v.85, #9)

Sections

Personal tools

Local resources

Archives of Toxicology (v.85, #9)