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Carcinogenic Potential (carcinogenic + potential)
Selected AbstractsCarcinogenic potential of commonly used hernia repair prostheses in an experimental modelBRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 3 2004P. Witherspoon Background: The purpose of this study was to assess the carcinogenic potential of commonly used hernia repair prostheses in an animal model. Methods: Three types of prosthetic material (monofilament polypropylene, multifilament polypropylene and expanded polytetrafluoroethylene) were implanted in CBA/H mice. Flat (1 cm2) and rolled pieces of the same material were placed subcutaneously in either flank, and a further flat piece was placed in the preperitoneal space. Owing to a high incidence of mesh extrusion in the polypropylene groups, the study protocol was modified to allow only preperitoneal placement of the material. A fourth, control, group had the pockets for the prostheses created but no material implanted. After modification of the protocol there were approximately 60 mice in each group. The mice were followed for 2 years, then killed and assessed histologically for tumour development. Results: No sarcoma developed at the site of mesh implantation in any of the groups. Conclusion: This study indicates that the risk of sarcoma formation at the site of hernia repair prostheses is very low. Copyright © 2004 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. [source] Effect of artificial mixtures of environmental polycyclic aromatic hydrocarbons present in coal tar, urban dust, and diesel exhaust particulates on MCF-7 cells in cultureENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 2 2004Brinda Mahadevan Abstract Human exposure to polycyclic aromatic hydrocarbons (PAHs) occurs through complex mixtures. The National Institute of Standards and Technology has established standard reference materials (SRMs) for selected PAH mixtures that are composed of carcinogenic, noncarcinogenic, and weakly carcinogenic compounds, such as those derived from coal tar (SRM 1597), atmospheric particulate matter (SRM 1649), and diesel particulate matter (SRM 1650). To study the effects of PAHs with different carcinogenic potential in complex mixtures, and to investigate the metabolic activation of noncarcinogenic and weakly carcinogenic PAHs to DNA-binding derivatives, artificial mixtures (1597H, 1649H, and 1650H) were prepared in the laboratory. These artificial mixtures contained the same relative ratios of noncarcinogenic and weakly carcinogenic PAHs present in SRM 1597, SRM 1649, and SRM 1650. The human mammary carcinoma-derived cell line MCF-7 was treated with these artificial mixtures and analyzed for PAH-DNA adduct formation and the induction of cytochrome P450 (CYP) enzymes. We found that the artificial mixtures formed lower but detectable levels of DNA adducts 24 and 48 hr after treatment than benzo[a]pyrene. Induction of CYP enzyme activity was measured by the ethoxyresorufin- O -deethylase assay, and the expression of CYP1A1 and CYP1B1 was confirmed by immunoblots. Both noncarcinogenic and weakly carcinogenic PAHs present in the artificial mixtures have the ability to induce CYP1A1 and CYP1B1 in MCF-7 cells and contribute to DNA binding. Therefore, it is necessary to take into account the noncarcinogenic and weakly carcinogenic PAHs present in environmental mixtures in assessing the potential risk associated with human exposure. Environ. Mol. Mutagen. 44:99,107, 2004. © 2004 Wiley-Liss, Inc. [source] Equivocal Colonic Carcinogenicity of Aloe arborescens Miller var. natalensis Berger at High-Dose Level in a Wistar Hannover Rat 2-y StudyJOURNAL OF FOOD SCIENCE, Issue 2 2009M. Yokohira ABSTRACT:, A 2-y carcinogenicity study of Aloe, Aloe arborescens Miller var. natalensis Berger, a food additive, was conducted for assessment of toxicity and carcinogenic potential in the diet at doses of 4% or 0.8% in groups of male and female Wistar Hannover rats. Both sexes receiving 4% showed diarrhea, with loss of body weight gain. The survival rate in the 4% female group was significantly increased compared with control females after 2 y. Hematological and biochemical examination showed increase of RBC, Hb, and Alb in the 4% males. The cause of these increases could conceivably have been dehydration through diarrhea. AST and Na were significantly decreased in the males receiving 4%, and Cl was significantly decreased in both 4% and 0.8% males. A/G was significantly increased in the 4% females, and Cl was significantly decreased (0.8%) in the female group. Histopathologically, both sexes receiving 4% showed severe sinus dilatation of ileocecal lymph nodes, and yellowish pigmentation of ileocecal lymph nodes and renal tubules. Adenomas or adenocarcinomas in the cecum, colon, and rectum were observed in 4% males but not in the 0.8% and control male groups. Similarly, in females, adenomas in the colon were also observed in the 4% but not 0.8% and control groups. In conclusion, Aloe, used as a food additive, exerted equivocal carcinogenic potential at 4% high-dose level on colon in the 2-y carcinogenicity study in rats. Aloe is not carcinogenic at nontoxic-dose levels and that carcinogenic potential in at 4% high-dose level on colon is probably due to irritation of the intestinal tract by diarrhea. [source] Attribution of tumour lethality and estimation of the time to onset of occult tumours in the absence of cause-of-death InformationJOURNAL OF THE ROYAL STATISTICAL SOCIETY: SERIES C (APPLIED STATISTICS), Issue 2 2000H. Ahn A new statistical approach is developed for estimating the carcinogenic potential of drugs and other chemical substances used by humans. Improved statistical methods are developed for rodent tumorigenicity assays that have interval sacrifices but not cause-of-death data. For such experiments, this paper proposes a nonparametric maximum likelihood estimation method for estimating the distributions of the time to onset of and the time to death from the tumour. The log-likelihood function is optimized using a constrained direct search procedure. Using the maximum likelihood estimators, the number of fatal tumours in an experiment can be imputed. By applying the procedure proposed to a real data set, the effect of calorie restriction is investigated. In this study, we found that calorie restriction delays the tumour onset time significantly for pituitary tumours. The present method can result in substantial economic savings by relieving the need for a case-by-case assignment of the cause of death or context of observation by pathologists. The ultimate goal of the method proposed is to use the imputed number of fatal tumours to modify Peto's International Agency for Research on Cancer test for application to tumorigenicity assays that lack cause-of-death data. [source] Polycyclic aromatic hydrocarbons in smoked cheeseJOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE, Issue 8 2008Marie Suchanová Abstract BACKGROUND: Polycyclic aromatic hydrocarbons (PAHs) represent a group of organic compounds containing two or more aromatic rings. Their control in the human food chain is required due to the mutagenic and carcinogenic potential, exhibited in vertebrates. In the present study, the occurrence of PAHs in 36 cheeses smoked by various processes was investigated. RESULTS: PAH concentrations (sum of 15 US EPA PAHs) found in samples smoked under controlled industrial conditions were at level 0.11 µg kg,1, whereas in ,home-made' cheeses, the PAH content was up to 10 times higher. A similar trend was observed for B[a]P, a marker compound representing carcinogenic PAHs. While its levels in commercial products prepared by controlled smoking technologies were close to the limit of quantification (0.03 µg kg,1); in household samples, the B[a]P content ranged from 0.6 to 0.9 µg kg,1. Significantly higher amounts of PAHs (up to three to six times) were found in surface layers as compared to internal parts of cheese. CONCLUSION: Although smoked cheese is a popular food, only several papers have focused on PAH levels in these products. This paper evaluates the contribution of different smoking technologies to PAH contamination of several cheeses and thus can help in a risk assessment associated with their consumption. Moreover, the study shows the concentration ratios of selected PAHs, from which the type of smoking technology can be indicated. The results obtained in this study also supported the suggestion of the EU Scientific Committee on Food to use benzo[a]pyrene as an indicator of the occurrence of higher-molecular mass PAHs. Copyright © 2008 Society of Chemical Industry [source] Assessment of carcinogenic potential of repeated fish fried oil in miceMOLECULAR CARCINOGENESIS, Issue 10 2006Manoj K. Pandey Abstract Our prior studies have shown that single topical treatment of repeated fish fried oil extract (RFFE), containing various polycyclic aromatic hydrocarbons (PAHs), to the dorsal epidermis of mice caused enhancement of DNA damage along with higher expression of p53 and p21WAF1 proteins and cell-cycle arrest. In the present study carcinogenic potential of repeated fish fried oil (RFFO) and RFFE was assessed. Single topical application of RFFO (100 µL/animal) and RFFE (100,500 µg/animal) to Swiss albino female mice resulted in significant induction (1.8- to 7.4-fold) of ornithine decarboxylase activity. Twice weekly topical application of methylcholanthrene (MCA) for 24 wk or single topical application of 7,12-dimethylbenzanthracene (DMBA) or RFFO or RFFE, as initiator followed by twice weekly application of 12-O-tetradecanoyl phorbol myristate acetate (TPA) as promoter for 24 wk, resulted in development of skin papillomas after 6, 7, 18, and 9 wk, respectively. The cumulative number of tumors in MCA, DMBA/TPA, RFFE (200 µg)/TPA, and RFFE (500 µg)/TPA groups were 276, 168, 34, and 58 after 24 wk while negligible or minimal initiating activity was noticed in RFFO/TPA group. No tumors were found in animals either given twice weekly topical application of RFFO or a single initiating dose of DMBA followed by twice weekly application of RFFO. Histopathology of skin of animals treated with RFFE/TPA showed marked proliferation of epidermal layers along with abnormal mitosis and multinucleated tumor appearance. Skin of animals in groups RFFO/TPA and DMBA/RFFO showed sloughing and regeneration of epidermal layers, oedema along with proliferation of fibroblasts. Histochemical localization of ,-glutamyl transpeptidase was found to be substantially higher in skin of mice treated with RFFO/TPA and RFFE/TPA. Animals treated with RFFO/TPA, DMBA/RFFO, and RFFE/TPA resulted in significant induction of cutaneous aryl hydrocarbon hydroxylase (AHH) (421,432%), ethoxyresorufin-O-deethylase (252,316%), and glutathione S-transferase (133,245%) activities. Animals treated with RFFO/TPA, DMBA/RFFO, and RFFE/TPA led to significant reduction in glutathione content (39,44%) with a concomitant increase in lipid peroxidation (254,492%). Animals treated with RFFO/TPA and RFFE/TPA led a significant decrease in catalase (43,69%) and superoxide dismutase (20,31%) activities while glutathione reductase activity was found to be diminished (23,51%) in RFFO, RFFO/TPA, DMBA/RFFO, and RFFE/TPA treated groups. These results suggest that RFFE possess skin tumor initiating activity and that it may have weak promoting activity as well, which may involve free radicals. © 2006 Wiley-Liss, Inc. [source] Colonic intra-epithelial carcinoma occurring in a hyperplastic polyp via a serrated adenomaPATHOLOGY INTERNATIONAL, Issue 3 2001Masanori Tanaka We present a case of intra-epithelial carcinoma occurring in a serrated adenoma of the colon. The pedunculated polyp, which measured 12 × 10 × 6 mm, was endoscopically removed from the ascending colon of a 78-year-old woman. Histologically, the polyp mainly consisted of serrated adenomatous glands, and had foci of intra-epithelial carcinoma at the top. Hyperplastic (metaplastic) areas were also present in both borders between the serrated adenomatous area and the surrounding normal mucosa. A sequential increase in the degree of dysplasia, and in the number of nuclei positively reactive for Ki-67 and p53 was evident from the hyperplastic areas toward the foci of carcinoma. The polyp described here may represent a carcinogenic potential of hyperplastic polyp via serrated adenoma. [source] Phototherapy and PUVA photochemotherapy in childrenPHOTODERMATOLOGY, PHOTOIMMUNOLOGY & PHOTOMEDICINE, Issue 2 2004S. A. Holme The use of phototherapy and photochemotherapy in children has been limited due to concerns over their long-term carcinogenic potential. Furthermore, the method of administration is disconcerting to some children, particularly as phototherapy treatment units are seldom rendered ,child-friendly'. Despite these reservations, ultra-violet therapies can be useful treatment options for children with selected dermatological conditions provided they are used under carefully controlled conditions. [source] Carcinogenicity study of GSM and DCS wireless communication signals in B6C3F1 miceBIOELECTROMAGNETICS, Issue 3 2007Thomas Tillmann Abstract The purpose of this study using a total of 1170 B6C3F1 mice was to detect and evaluate possible carcinogenic effects in mice exposed to radio-frequency-radiation (RFR) from Global System for Mobile Communication (GSM) and Digital Personal Communications System (DCS) handsets as emitted by handsets operating in the center of the communication band, that is, at 902 MHz (GSM) and 1747 MHz (DCS). Restrained mice were exposed for 2 h per day, 5 days per week over a period of 2 years to three different whole-body averaged specific absorption rate (SAR) levels of 0.4, 1.3, 4.0 mW/g bw (SAR), or were sham exposed. Regarding the organ-related tumor incidence, pairwise Fisher's test did not show any significant increase in the incidence of any particular tumor type in the RF exposed groups as compared to the sham exposed group. Interestingly, while the incidences of hepatocellular carcinomas were similar in EMF and sham exposed groups, in both studies the incidences of liver adenomas in males decreased with increasing dose levels; the incidences in the high dose groups were statistically significantly different from those in the sham exposed groups. Comparison to published tumor rates in untreated mice revealed that the observed tumor rates were within the range of historical control data. In conclusion, the present study produced no evidence that the exposure of male and female B6C3F1 mice to wireless GSM and DCS radio frequency signals at a whole body absorption rate of up to 4.0 W/kg resulted in any adverse health effect or had any cumulative influence on the incidence or severity of neoplastic and non-neoplastic background lesions, and thus the study did not provide any evidence of RF possessing a carcinogenic potential. Bioelectromagnetics 28:173,187, 2007. © 2006 Wiley-Liss, Inc. [source] The challenge of follow-up in narrowband ultraviolet B phototherapyBRITISH JOURNAL OF DERMATOLOGY, Issue 2 2007B.L. Diffey Summary Background, The use of narrowband ultraviolet (UV) B phototherapy to treat psoriasis and other disorders has increased markedly since the TL-01 lamps were introduced in the 1980s. While broadband UVB phototherapy has generally been considered to be a relatively safe treatment, some concern has been raised about the potential increased skin cancer risk with narrowband UVB. Objectives, The likelihood of a patient who is free of nonmelanoma skin cancer (NMSC) at the start of phototherapy developing a malignancy after a certain follow-up period will be dependent not only on the carcinogenic potential of the treatment but also on the age-conditional probability of natural occurrence. We were interested to explore the potential difficulty of designing studies to separate these two events. Methods, Mathematical models were developed that combined age-conditional probabilities of developing NMSC due to natural causes with the risk of inducing these cancers from narrowband UVB phototherapy in order to estimate the excess number of cancers resulting from this therapeutic intervention in a cohort of patients. Results, Within-department studies will be most unlikely to demonstrate that the number of NMSCs observed in follow-up studies is significantly different from that expected in an untreated population, even for a follow-up period of 20 years. Conclusions, Determination of the carcinogenic potential associated with narrowband UVB will require large multicentre studies typically involving several thousand new patients per year and followed up for 10 years or more. [source] Carcinogenic potential of commonly used hernia repair prostheses in an experimental modelBRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 3 2004P. Witherspoon Background: The purpose of this study was to assess the carcinogenic potential of commonly used hernia repair prostheses in an animal model. Methods: Three types of prosthetic material (monofilament polypropylene, multifilament polypropylene and expanded polytetrafluoroethylene) were implanted in CBA/H mice. Flat (1 cm2) and rolled pieces of the same material were placed subcutaneously in either flank, and a further flat piece was placed in the preperitoneal space. Owing to a high incidence of mesh extrusion in the polypropylene groups, the study protocol was modified to allow only preperitoneal placement of the material. A fourth, control, group had the pockets for the prostheses created but no material implanted. After modification of the protocol there were approximately 60 mice in each group. The mice were followed for 2 years, then killed and assessed histologically for tumour development. Results: No sarcoma developed at the site of mesh implantation in any of the groups. Conclusion: This study indicates that the risk of sarcoma formation at the site of hernia repair prostheses is very low. Copyright © 2004 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. [source] A medium-term rat liver bioassay for rapid in vivo detection of carcinogenic potential of chemicalsCANCER SCIENCE, Issue 1 2003Nobuyuki Lto A reliable medium-term bioassay system for rapid detection of carcinogenic potential of chemicals in the human environment has been developed. The 8-week-protocol consists of 2 stages; male F344 rats are given a single intraperitoneal injection of diethylnitrosamine (200 mg/kg) for initiation of liver carcinogenesis, followed by a 6-week test chemical treatment starting 2 weeks thereafter. Test chemicals are usually given in the diet or the drinking water and in the 2nd week of test chemical treatment, all rats are subjected to two-thirds partial hepatectomy in order to induce regenerative cell replication. The end-point marker is the glutathione S-transferase placental form (GST-P)-positive hepatic focus, the numbers and sizes of which are analyzed using an image-analyzer and expressed as values per unit liver section (1 cm2). When the yield of GST-P-positive foci is significantly enhanced (P<0.05) over the control value, a chemical is judged to possess carcinogenic or promotion potential for the liver. Among 313 chemicals already tested in this system in our laboratory, 30/31 (97%) mutagenic hepatocarcinogens and 29/33 (88%) non-mutagenic hepatocarcinogens gave positive results. Ten out of 43 (23%) agents known to be carcinogenic in organs other than the liver were also positive. It is particularly important that only one of 48 non-carcinogens gave a very weak positive result, so that the system has a very low false-positivity rate. It is now well documented that the assay system is highly effective for detecting hepatocarcinogens, bridging the gap between traditional long-term carcinogenicity tests and short-term screening assays. At the Fourth International Conference on Harmonization, our medium-term liver bioassay based on an initiation and promotion protocol was recommended in the guidelines as an acceptable alternative to the long-term rodent carcinogenicity test. (Cancer Sci 2003; 94: 3,8) [source] Thorium X treatment: multiple basal cell carcinomas within a port-wine stainCLINICAL & EXPERIMENTAL DERMATOLOGY, Issue 5 2009J. Natkunarajah Summary Thorium X is an ionizing radiation treatment that was commonly used by dermatologists in the 1930 s to 1950 s to treat a variety of benign dermatoses and vascular lesions including port-wine stains. By the 1960 s, thorium X was discontinued due to poor clinical results and the carcinogenic potential. We report a 64-year-old man with a history of multiple basal cell carcinomas in a facial port wine stain, which had previously been treated with thorium X. [source] | ||||||||||||||||||||||||||||