Food and Chemical Toxicology

Our medical research library holds 17 studies published in Food and Chemical Toxicology (1983–2018). Each entry links to the study's record on PubMed and, where there is one, to the publisher's page and a free full text. 15 have an abstract, the authors' own summary as PubMed records it: open "Abstract" to read it.

About the journal

• Publisher: Elsevier Science Ltd
• Published: 1982 to the present, England
• Language: English
• ISSN: 0278-6915 (print), 1873-6351 (electronic)
• Continues: Food and Cosmetics Toxicology
• Its record in the NLM Catalog

2010s

• Dexamethasone alleviates pemetrexed-induced senescence in Non-Small-Cell Lung Cancer. H. Ge, J. Ke, N. Xu, et al. 2018;119:86-97. PubMed · Publisher

  Abstract

  Pemetrexed (PEM) is a novel and multi-targeted antifolate used as an antineoplastic agent for non-small cell lung cancer (NSCLC) and pleural mesothelioma. Although glucocorticoid was often used with PEM to reduce toxicity during the chemotherapy, it is not clear yet whether glucocorticoid co-administration could affect PEM efficacy in NSCLC. Here we established NSCLC cell lines and examined the effects of dexamethasone (DEX) on PEM sensitivity in vitro and in xenograft models. DEX co-administration reduced chemotherapy sensitivity to PEM in xenograft models. DEX co-administration promoted cell growth and weakened senescence growth arrest, such as altered secretions of proinflammatory and mitogenic cytokines, reminiscent of a senescence associate secretory phenotype (SASP). CSCs in DEX co-administration group were subsequently found to be less sensitive towards PEM treatment as measured by cell proliferation and generation of tumor spheres in the presence of PEM. Survival molecule B-cell lymphoma-2 (Bcl-2) may involve in this process and blockage of Bcl-2 could reverse altered senescence and CSCs abilities, thus alleviated PEM insensitivity. As such, DEX might suppress the antitumor activity of PEM through altered SASP level that had induced traits similar to CSCs.

  Copyright © 2018 Elsevier Ltd. All rights reserved.

• Low dose assessment of the carcinogenicity of furan in male F344/N Nctr rats in a 2-year gavage study. L.S. Von Tungeln, N.J. Walker, G.R. Olson, et al. 2017;99:170-181. PubMed · Publisher · Free full text

  Abstract

  Furan is a volatile organic chemical that is a contaminant in many common foods. Furan is hepatocarcinogenic in mice and rats; however, the risk to humans from dietary exposure to furan cannot be estimated accurately because the lowest tested dose of furan in a 2-year bioassay in rats gave nearly a 100% incidence of cholangiocarcinoma. To provide bioassay data that can be used in preparing risk assessments, the carcinogenicity of furan was determined in male F344/N Nctr rats administered 0, 0.02, 0.044, 0.092, 0.2, 0.44, 0.92, and 2 mg furan/kg body weight (BW) by gavage 5 days/week for 2 years. Exposure to furan was associated with the development of malignant mesothelioma on membranes surrounding the epididymis and on the testicular tunics, with the increase being significant at 2 mg furan/kg BW. There was also a dose-related increase in the incidence of mononuclear cell leukemia, with the increase in incidence being significant at 0.092, 0.2, 0.92, and 2 mg furan/kg BW. Dose-related non-neoplastic liver lesions included cholangiofibrosis, mixed cell foci, basophilic foci, biliary tract hyperplasia, oval cell hyperplasia, regenerative hyperplasia, and cytoplasmic vacuolization. The most sensitive non-neoplastic lesion was cholangiofibrosis, the frequency of which increased significantly at 0.2 mg furan/kg BW.

  Published by Elsevier Ltd.

• Cisplatin and resveratrol induce apoptosis and autophagy following oxidative stress in malignant mesothelioma cells. Y.J. Lee, G.J. Lee, S.S. Yi, et al. 2016;97:96-107. PubMed · Publisher

  Abstract

  Malignant mesothelioma (MM) is characterized by poor responsiveness to current chemotherapeutic drugs, usually owing to high resistance to apoptosis. Here, we investigated chemosensitizing effects of phytochemical resveratrol, in combination with cisplatin, on MM cells. The combination treatment of cisplatin and resveratrol (CDDP/RSV) synergistically induced apoptosis, as evidenced by typical cell morphological changes, the appearance of sub-G0/G1 peak, an increase in the Annexin V(+) cells and the cleavage of caspase-3 and PARP. CDDP/RSV increased ROS production and depolarization of mitochondrial membrane potential with an increase in the Bax/Bcl-2 ratio. These changes were attenuated by pretreatment with N-acetylcysteine, suggesting that CDDP/RSV induced apoptosis through oxidative mitochondrial damage. Compared with MSTO-211H cells, CDDP/RSV was less efficient in killing H-2452 cells. H-2452 cells exhibited an enhanced autophagy to CDDP/RSV, as observed by an increase in viable cells exhibiting intense LysoTracker Red staining and up-regulation of Beclin-1 and LC3A. Inhibition of autophagy by bafilomycin A1 rendered cells more sensitive to CDDP/RSV-induced cytotoxicity and this was associated with induction of apoptosis. These data indicate that the increased resistance of H-2452 cells to CDDP/RSV is closely related to the activation of self-defensive autophagy, and provide the rationale for targeting the autophagy regulation in the treatment of MM.

  Copyright © 2016 Elsevier Ltd. All rights reserved.

• Resveratrol and cisplatin in a malignant mesothelioma cell model. S. Chirumbolo, G. Bjørklund. 2016;98(Pt B):308-309. Letter PubMed · Publisher

• Resveratrol contributes to chemosensitivity of malignant mesothelioma cells with activation of p53. Y.J. Lee, I.S. Park, Y.J. Lee, et al. 2014;63:153-60. PubMed · Publisher

  Abstract

  Resveratrol is a naturally occurring polyphenolic phytoalexin with chemopreventive properties. We previously reported a synergistic anti-proliferative effect of resveratrol and clofarabine against malignant mesothelioma (MM) cells. Here, we further investigated molecular mechanisms involved in the synergistic interaction of these compounds in MM MSTO-211H cells. Resveratrol, in combination with clofarabine, time-dependently induced a strong cytotoxic effect with the nuclear accumulation of phospho-p53 (p-p53) in MSTO-211H cells, but not in normal mesothelial MeT-5A cells. Combination treatment up-regulated the levels of p-p53, cleaved caspase-3, and cleaved PARP proteins. Gene silencing with p53-targeting siRNA attenuated the sensitivity of cells to the combined treatment of two compounds. Analyses of p53 DNA binding assay, p53 reporter gene assay, and RTP-CR toward p53-regulated genes, including Bax, PUMA, Noxa and p21, demonstrated that induced p-p53 is transcriptionally active. These results were further confirmed by the siRNA-mediated knockdown of p53 gene. Combination treatment significantly caused the accumulation of cells at G1 phase with the increases in the sub-G0/G1 peak, DNA ladder, nuclear fragmentation, and caspase-3/7 activity. Taken together, these results demonstrate that resveratrol and clofarabine synergistically elicit apoptotic signal via a p53-dependent pathway, and provide a scientific rationale for clinical evaluation of resveratrol as a promising chemopotentiator in MM.

  Copyright © 2013 Elsevier Ltd. All rights reserved.

• Species and gender differences in the carcinogenic activity of trimethylolpropane triacrylate in rats and mice. I. Surh, D.B. Rao, M.F. Cesta, et al. 2014;66:254-61. PubMed · Publisher · Free full text

  Abstract

  Trimethylolpropane triacrylate (TMPTA) is a multifunctional monomer with industrial applications. To determine the carcinogenic potential, male and female F344/N rats and B6C3F1/N mice were administered TMPTA (0, 0.3, 1.0, or 3.0mg/kg) in acetone dermally for 2 years. There were no differences in the body weights and survival in the treated animals compared to controls. Nonneoplastic skin lesions at the site of application included epidermal hyperplasia and hyperkeratosis in both rats and mice. There were no incidences of tumors at the site of application in rats and mice. Rare malignant liver neoplasms were observed in female mice that included hepatoblastoma in the 0.3 and 3.0mg/kg groups, and hepatocholangiocarcinoma in the 1.0 and 3.0mg/kg groups. The incidences of uterine stromal polyp and stromal polyp or stromal sarcoma (combined) in female mice occurred with positive trends and the incidences were significantly increased in the 3.0mg/kg group. A marginal increase in the incidences of malignant mesothelioma in male rats may have been related to TMPTA treatment. In conclusion, our studies show that TMPTA is a dermal irritant in both rats and mice of either sex. Increased incidences of tumor formation were observed in female mice and male rats.

  Published by Elsevier Ltd.

• Synergistic anti-cancer effects of resveratrol and chemotherapeutic agent clofarabine against human malignant mesothelioma MSTO-211H cells. Y.J. Lee, Y.J. Lee, J.H. Im, et al. 2013;52:61-8. PubMed · Publisher

  Abstract

  Dietary phytochemicals as adjuvants have been suggested to play important roles in enhancing chemotherapeutic potential owing to multitargeted chemopreventive properties and lack of substantial toxicity. Here, we investigated the efficacy of the combined treatment of various phytochemicals with the anticancer drug clofarabine in malignant mesothelioma MSTO-211H cells and normal mesothelial MeT-5A cells. The combined treatment of resveratrol and clofarabine produced a synergistic antiproliferative effect in MSTO-211H cells, but not in MeT-5A cells. In MSTO-211H cells, the nuclear accumulation of Sp1 and the levels of p-Akt, Sp1, c-Met, cyclin D1, and p21 were effectively decreased by the combined treatment of them. In combination with clofarabine, the ability of resveratrol to reduce the contents of Sp1 and its target gene products was also evident in a time- and dose-dependent experiment. The inhibition of phosphoinositide 3-kinase using Ly294002 augmented a decrease in the p21 level induced by their combination, but it showed no significant effects on expression of Sp1 and cyclin D1. Taken together, the data provide evidence that the synergistic antiproliferative effect of resveratrol and clofarabine is linked to the inhibition of Akt and Sp1 activities, and suggest that this combination may have therapeutic value in treatment of malignant mesothelioma.

  Copyright © 2012 Elsevier Ltd. All rights reserved.

• Reactive oxygen species and PI3K/Akt signaling play key roles in the induction of Nrf2-driven heme oxygenase-1 expression in sulforaphane-treated human mesothelioma MSTO-211H cells. Y.J. Lee, H.Y. Jeong, Y.B. Kim, et al. 2012;50(2):116-23. PubMed · Publisher

  Abstract

  The nuclear factor erythroid-derived 2 related factor 2 (Nrf2)/heme oxygenase (HO)-1 induction plays cytoprotective roles against oxidative injury, apoptosis, and anticancer therapy; however, little is known about its regulation in human mesothelioma MSTO-211H cells. In this study, we investigated Nrf2/HO-1 induction in response to sulforaphane and determined the signaling pathways involved in this process. Sulforaphane treatment decreased cell viability and triggered a rapid and transient increase in the intracellular ROS levels. Pretreatment with N-acetylcysteine (NAC) prevented sulforaphane-induced cytotoxicity. Erk1/2 was activated within 1h of sulforaphane addition, whereas Akt phosphorylation was suppressed until the first 8h, and was then maintained at an elevated level until 72h, displaying a biphasic regulatory feature. Nrf2 protein levels in both nuclear and whole cell lysates were increased after sulforaphane treatment and were decreased by pretreatment with NAC, actinomycin D and cycloheximide. Activation of the Nrf2/HO-1 system after sulforaphane treatment was suppressed by pretreatment with NAC or Ly294002, a PI3K inhibitor. Knockdown of Nrf2 with siRNA decreased cell viability and attenuated sulforaphane-induced HO-1 up-regulation. Overall, our results indicate that ROS generation and/or activation of PI3K/Akt signaling regulate cell survival and Nrf2-driven HO-1 expression in sulforaphane-treated MSTO-211H cells.

  Copyright © 2011 Elsevier Ltd. All rights reserved.

2000s

• Promotion of morphological transformation by Di-n-butyltin dichloride in C3H/10T1/2 cells: prediction by prior expression of tumour promoter-responsive genes. C.L. Parfett, T. Marquardt, R. Pilon. 2000;38(4):339-49. PubMed · Publisher

  Abstract

  Previous studies in our laboratory have shown that chemical treatments may induce increases in proliferin gene family mRNA accumulation in cultured murine embryonic cells. Proliferin inductions are highly correlated with subsequent promotional outcomes during two-stage focus-formation assays in C3H/10T1/2 cell cultures. In work reported here, the strong affiliation between these two responses was further validated after treating cells with di-n-butyltin dichloride which is a polyvinyl chloride (PVC) plastic additive that often contaminates food and water. Increased proliferin expression and promotion of morphological transformation occurred at similar concentrations. Promotion of transformation was detected at di-n-butyltin dichloride concentrations of 80 nM (24 ng/ml) and above, if added to initiated cultures before confluent monolayers had formed. Proliferin induction and morphological transformation were both reduced in confluent cultures treated with di-n-butyltin dichloride, as compared to subconfluent cultures. Proliferin expression measured in near-confluent cultures was induced up to 10-fold during the 36-hr period following di-n-butyltin dichloride exposure and was accompanied by increased accumulation of transcripts from many genes regulated by oxidative stresses, growth-inducing agents, and/or other promoting agents (asbestos, superoxide radicals ). Di-n-butyltin dichloride-induced mRNA species included members of the fos and jun proto-oncogene families, c-myc, egr1, ribonucleotide reductase (R2 subunit), odc, macrophage chemotactic protein/je, hsp70, metallothionine IIA, c-sod and mn-sod. The observed patterns of RNA accumulation suggested that a small subset of mRNA species, including proliferin, exhibit regulatory behaviour as a response to dissimilar agents or conditions that promote focus-formation in C3H/10T1/2 cultures. Plausible predictions of promotional effects in two-stage morphological transformation assays can be made from gene-expression responses to test agents.

1990s

• Augmentation of chrysotile-induced oxidative stress by BHA in mice lungs. I. Ahmad, K. Krishnamurthi, J.M. Arif, et al. 1995;33(3):209-15. PubMed · Publisher

  Abstract

  Asbestos is known to induce oxidative stress in the lung. The consumption of butylated hydroxyanisole (BHA) in preserved food and soft drinks is increasing in the general population, which includes workers in asbestos factories. Because there is no information on the effect of co-exposure to chrysotile and BHA, the time-dependent effects of a single intratracheal dose of chrysotile (1 mg per mouse) and a single ip dose of BHA (350 mg/kg body weight) on various indices of oxidative stress such as lipid peroxidation, hydrogen peroxide generation, glutathione peroxidase (GPX), glutathione reductase (GR), catalase, glucose-6-phosphate dehydrogenase (G6PDH) and glutathione (GSH) were followed for up to 14 days. Microsomal lipid peroxidation (as well as that induced by NADPH) was significantly enhanced by BHA in the chrysotile-exposed group. GPX and GR activities in the same group were gradually decreased by BHA. Non-significant modulation of catalase activity by BHA was also noted. BHA induces GSH to a significant extent in lungs exposed with chrysotile. An increase in the G6PDH activity was maximal (19%; P < 0.05) at day 3. The results clearly demonstrate that BHA enhances chrysotile-induced oxidative stress in the lung.

1980s

• Asbestos: toxicology and risk assessment for the general population in The Netherlands. G.K. Montizaan, A.G. Knaap, C.A. Van der Heijden. 1989;27(1):53-63. Review PubMed · Publisher

  Abstract

  Within the scope of the preparation of Integrated Criteria Documents for priority compounds in The Netherlands, the possible health effects of oral and inhalatory exposure to asbestos for the general population were evaluated. It was concluded from the results of experiments in animals that exposure to asbestos by the oral route is not carcinogenic and is not expected to present a health risk to the general population. Inhaled asbestos, however, is distinctly carcinogenic to man, giving rise to lung tumours, and mesotheliomas of the pleura and peritoneum. Chrysotile asbestos appears to be less potent in inducing mesotheliomas than the amphiboles, but all types of asbestos appear to have a similar potency for inducing lung cancer. The risk of mesothelioma is not expected to be influenced by smoking, whereas the risk of lung cancer is expected to be ten times higher in smokers than in non-smokers exposed to the same asbestos concentrations. Risk-assessment models for the inhalatory route, for the general population, are based on linear non-threshold extrapolation of occupational exposure to much lower environmental concentrations. These models give only a rough approximation of the risk of environmental exposure to asbestos. In accordance with the Air Quality Guidelines of the World Health Organization (World Health Organization, 1987), it was estimated that an extra risk of lung cancer of one in 10(6) (in the general population, with 30% smokers) may be presented by lifetime exposure to asbestos fibres longer than 5 microns, measured by electron microscopy, at concentrations of 100-1000/m3. It was further estimated that an extra risk of mesothelioma of one in 10(6) may be presented by lifetime exposure to 10-100 amphibole fibres/m3 or to a range of 100-10000 chrysotile fibres/m3 (fibres longer than 5 microns). From the current asbestos concentrations, the risk of mesothelioma for the general population in The Netherlands appears to be negligible; the extra risk of lung cancer is expected to be higher than 1 in 10(6) near asbestos sources, whereas it appears to be negligible in background areas and in most large cities and industrial areas. However, it must be borne in mind that the validity of the risk figures given is difficult to judge.

• Intestinal transport of some macromolecules in food. M.L. Weiner. 1988;26(10):867-80. Review PubMed · Publisher

  Abstract

  This review focuses on the intestinal transport of macromolecules in food. Although it is known that neonates have the ability to absorb proteins from the intestine as a means of passive immunization, it has generally been assumed that adults do not retain this capability. A number of studies have shown that the adult mammalian small intestine is capable of transporting a variety of macromolecules in food to a very limited extent. The evidence demonstrating the transport of test substances in the micron-size range across the adult intestinal epithelial barrier is examined for a number of food substances and environmental contaminants. It will be shown that macromolecules can be transported across this barrier by endocytosis; by uptake into the gut-associated lymphoid tissue, and possibly by uptake into the goblet cells. It is considered highly unlikely that large micron-sized particles pass between intestinal cells due to the integrity of the tight junctions between cells that exclude particles in this size range. Quantitative estimates for macromolecular uptake are included along with a discussion of the physiological parameters influencing macromolecular transport.

• An in vitro lung epithelial cell system for evaluating the potential toxicity of inhalable materials. A.P. Li. 1986;24(6-7):527-34. PubMed · Publisher

  Abstract

  Assays have been developed using a lung epithelial cell strain, LEC, for evaluating the cytotoxicity and genotoxicity of gases, vapours, particles and fibres. LEC was derived from an adult male Fischer 344 rat and was cultured continuously in vitro for over 60 passages. The cells had an epithelial morphology, a near-diploid modal chromosome number of 43-44, and properties of untransformed cells. Lamellar inclusion bodies were found in the cytoplasm, suggesting that LEC originated from the type II alveolar cells. The ability to LEC to metabolize xenobiotics was demonstrated by the formation of polar metabolites from benzo[a]pyrene, the induction of gene mutation by promutagens in a metabolically incompetent cell line (Chinese hamster ovary cells) after co-cultivation with LEC, and the induction of sister chromatid exchange in LEC by promutagens. LEC will grow on collagen gel in the absence of an overlying medium, thereby constituting an in vitro exposure system closely resembling lung epithelium in vivo. The cytotoxic potential of inhalable agents, including nitrogen dioxide, phenol vapours, formaldehyde, automobile exhaust, titanium dioxide and chrysotile and crocidolite forms of asbestos was studied. The in vitro cytotoxicity appeared to correlate well with the known in vivo pulmonary toxicity of the substances studied. Using chromosomal-aberration induction as an endpoint, chrysotile asbestos was found to be genotoxic to LEC. Our results suggest that LEC may be a useful in vitro system for the evaluation of the toxic potential of inhalable materials.

• Genotoxicity of chemical and physical agents in cultured human tissues and cells. A. Weston, S.M. Plummer, R.C. Grafstrom, et al. 1986;24(6-7):675-9. PubMed · Publisher

  Abstract

  In vitro model systems have recently been developed to investigate the toxicity of chemical, microbial and physical agents in normal human tissues and cells from many of the major tissue sites of high cancer incidence. Pathobiological endpoints used in these studies include alterations in incorporation rates of precursors into DNA, RNA and protein, in the clonal growth rate of cultured cells and in DNA structure (e.g. single-strand breaks, DNA-protein crosslinks and chemical-DNA adducts) and the induction of differentiation, chromosomal and karyotypic abnormalities, mutations and neoplastic transformation. These systems have been used to study a variety of complex mixtures and individual substances, including cigarette smoke components such as benzo[a]pyrene and N-nitrosamines, formaldehyde, fecapentaenes, asbestos, and nickel and chromium ions. In addition, increasing awareness of the role of oncogenes in human carcinogenesis has led to studies involving transfection experiments with oncogenes and hepatitis B viral genes in normal human cells.

• In vitro correlates of mineral dust toxicity. R.C. Brown, A. Poole, C.J. Turver. 1986;24(6-7):535-8. PubMed · Publisher

  Abstract

  In vitro studies of mineral fibres have shown that these materials are capable of causing the production of free radical damage (measured by the accumulation of thiobarbituric acid-reactive material) in a way that does not depend on fibre morphology but rather on a surface property, probably the presence of iron. The DNA-damaging activities of the same dusts were measured in an assay based on the production of single-stranded DNA. Activity in this assay was again not dependent on the presence of fibres. In contrast the cytotoxicity of mineral fibres towards V79-4 cells correlated better with in vivo tumorigenicity than did either of the above activities. The activity of fibres against a macrophage-like cell demonstrated that both fibre morphology and chemical properties are important determinants of biological activity.

• Epidemiological studies on ingested asbestos. J. Hopkins. 1984;22(2):179-8l. PubMed · Publisher

• An investigation of the penetration of ingested asbestos into the normal and abnormal intestinal mucosa of the rat. M.E. Meek, P. Grasso. 1983;21(2):193-200. PubMed · Publisher

  Abstract

  To characterize the tissue response associated with the presence of asbestos fibres in the gastro-intestinal wall, duodenal tissues of Wistar rats were examined by light microscopy following injection of a suspension containing amosite fibres into the wall of the duodenum. Intestinal tissues were also examined by light microscopy following oral administration of amosite for 5 days to healthy animals and for up to 7 days to animals with induced gastro-intestinal ulcers. Injection of amosite into the wall of the gastro-intestinal tract resulted in granulomatous lesions characterized by large numbers of macrophages containing crystals with the polarizing characteristics of amosite fibres. Examination by polarizing light microscopy following ingestion of asbestos revealed no such lesions or other histopathological abnormalities in the gut wall of the healthy animals and no intracellular fibres were observed in the animals with ulcers. Light microscopy, therefore, yielded no pathological evidence of widespread transmigration of asbestos from the gastro-intestinal tract of rats, even under conditions of mucosal loss. Further studies involving analysis by electron microscopy are under way.

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