An investigation of factors contributing to styrene and styrene-7,8-oxide exposures in the reinforced-plastics industry.
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During the manufacturing of reinforced plastics, large amounts of styrene and trace quantities of styrene-7,8-oxide (SO) are released. Since previous work suggests that inhalation of even small amounts of SO might be an important health risk, we investigated several possible factors contributing to styrene and SO exposure during the manufacture of reinforced plastics. Factors related to job type, worker and the type and quantity of styrene-containing resins were investigated using mixed-effects multiple linear regression models. Overall, SO exposure levels were positively correlated with styrene exposure levels. However, this correlation was statistically significant only among hand laminators who had the highest exposures to both styrene and SO. An important factor for predicting both styrene and SO concentrations was the type of resin used, while the quantity of resin consumed was predictive of styrene but not of SO exposure. Since So exposure appears to be associated with factors other than coexposure to styrene, more effort should be placed on investigating emissions of SO per se. The type of mixed-models regression analysis employed in this study can be used for clarifying the underlying patterns for exposures to styrene and SO as well as for evaluating preventive measures. (+info)
Determination of an optimal dosing regimen for aspirin chemoprevention of 1,2-dimethylhydrazine-induced colon tumours in rats.
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In order to establish an optimal timing and duration of aspirin treatment in the chemoprevention of 1,2-dimethylhydrazine (DMH)-induced colon cancer in rats, colon tumours were induced using an established protocol and aspirin was given in the diet at 500 p.p.m. during various stages of colon carcinogenesis. Results indicate that only aspirin treatment throughout the entire carcinogenic period significantly reduced tumour incidence and volume whereas intermittent aspirin dosing increased tumour number and/or volume, suggesting that aspirin must be used for an extended period in order to gain any chemopreventive benefit. (+info)
Environmental pathology: new directions and opportunities.
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The National Institute of Environmental Health Sciences (NIEHS) supports a number of training programs for predoctoral and postdoctoral (D.V.M., M.D., Ph.D.) fellows in toxicology, epidemiology and biostatistics, and environmental pathology. At the Experimental Biology meeting in April 1997, the American Society of Investigative Pathology (ASIP) sponsored a workshop including directors, trainees, and other interested scientists from several environmental pathology programs in medical and veterinary colleges. This workshop and a related session on "Novel Cell Imaging Techniques for Detection of Cell Injury" revealed advances in molecular and cell imaging approaches as reviewed below that have a wide applicability to toxicologic pathology. (+info)
Pathological evaluation of the effects of intentional disocclusion and overloading occlusion in odontogenesis disorders in N-methylnitrosourea-treated hamsters.
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This study compares the effects of disocclusion and overloading occlusion on dental lesions. Ten-day-old Syrian hamsters were divided into 4 groups: group I, untreated animals; group II, animals whose hemilateral incisors were disoccluded; group III, N-methylnitrosourea (MNU)-treated animals; and group IV, MNU-treated animals whose hemilateral incisors were disoccluded. The ipsilateral maxillary and mandibular incisors were repetitively cut with diamond discs. The hamster is easier to anesthetize. Animals received a 0.2% solution of MNU (10 mg/kg body weight) intragastrically twice a week for 16 wk. All the cut mandibular incisors and the MNU-treated uncut mandibular incisors showed lack of iron deposition on the enamel surface. The eruption rate was significantly higher in the cut disoccluded incisors of groups II and IV (p < 0.05) and significantly lower in the uncut overloaded incisors of groups II and IV (p < 0.05). In the cut mandibular incisors of group IV, the degree of the disturbance of odontogenesis and the atypical proliferation of odontogenic epithelium were more prominent (p < 0.02), and the dental lesions occurred earlier. Histologically, the disturbed Hertwig's epithelial sheath and the Hertwig's epithelial sheath-like transformed U-shaped part and enamel organ seemed to lead to disturbances of amelogenesis and detinogenesis as well as to atypical proliferation of odontogenic epithelium nests. Thus, this method of disocclusion of the incisors of rodents may represent a useful model for the investigation of the effects of various agents on tooth formation over a short experimental period. (+info)
Marriage of a medium-term liver model to surrogate markers--a practical approach for risk and benefit assessment.
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The need for a reliable medium-term alternative to traditional long-term rodent test protocols for carcinogen risk assessment is pressing given the immense variety of compounds being developed for introduction into the human environment. The established lack of a complete correlation between mutagenicity and carcinogenicity means that recourse must be made to an in vivo model. Optimally, this model should be able to detect not only complete carcinogenic or promoting potential but also any ability to inhibit neoplasia. In order to be effective, it must take into account the available detailed knowledge on mechanisms of action of carcinogens and modulating agents. The Ito model, for which a uniquely comprehensive set of background data has already been accumulated, has a solid scientific basis; this model utilizes quantitative data for glutathione S transferase-positive foci as the preneoplasia-based surrogate end point (PSE). A very practical candidate for routine application, its predictive power, its flexibility, and its capacity to incorporate a range of mechanism-based surrogate end points (MSEs) provide a powerful tool for attainment of the twin goals of detecting carcinogenic agents and identifying promising chemopreventors. (+info)
Differential patterns of response to doxycycline and transforming growth factor beta1 in the down-regulation of collagenases in osteoarthritic and normal human chondrocytes.
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OBJECTIVE: To investigate the ability of doxycycline, transforming growth factor beta1 (TGFbeta1), and phorbol myristate acetate (PMA) to modulate collagenase synthesis in osteoarthritic (OA) chondrocytes. METHODS: Levels of fibroblast collagenase (matrix metalloproteinase 1 [MMP-1]), neutrophil collagenase (MMP-8), and collagenase 3 (MMP-13) proteins and messenger RNA (mRNA) were measured in chondrocytes isolated from involved and uninvolved areas of OA cartilage and from normal human chondrocytes, after treatment with doxycycline, TGFbeta1, and PMA. RESULTS: Chondrocytes isolated from cartilage immediately adjacent to the OA lesion had, on average, 1.8-3.9-fold higher basal levels of MMP mRNA. These cells down-regulated collagenase proteins and mRNA upon incubation with TGFbeta1. In contrast, chondrocytes from areas located more distant from the macroscopic lesion increased MMP-13 mRNA, while MMP-1 and MMP-8 decreased after stimulation with TGFbeta1. Discoordinate regulation was observed after stimulation with PMA, with an increase in MMP-1 and MMP-8 but a decrease in MMP-13. Incubation of OA chondrocytes with doxycycline (1-10 microg/ml), at pharmacologically achievable levels, decreased levels of mRNA of all 3 collagenases, but not G3PDH. In addition, doxycycline inhibited the increase in mRNA for these enzymes in normal chondrocytes stimulated with tumor necrosis factor alpha. CONCLUSION: These findings suggest that regulation of MMP-1, MMP-8, and MMP-13 in OA chondrocytes, although mediated by differing pathways, can be decreased by treatment with doxycycline at low concentrations. Our data provide a rationale for the use of doxycycline in the treatment of OA. (+info)
Asbestos induces activator protein-1 transactivation in transgenic mice.
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Activation of activator protein (AP-1) by crocidolite asbestos was examined in vitro in a JB6 P+ cell line stably transfected with AP-1-luciferase reporter plasmid and in vivo using AP-1-luciferase reporter transgenic mice. In in vitro studies, crocidolite asbestos caused a dose- and time-dependent induction of AP-1 activation in cultured JB6 cells. The elevated AP-1 activity persisted for at least 48 h. Crocidolite asbestos also induced AP-1 transactivation in the pulmonary and bronchial tissues of transgenic mice. AP-1 activation was observed at 2 days after intratracheal instillation of the mice with asbestos. At 3 days postexposure, AP-1 activation was elevated 10-fold in the lung tissue and 22-fold in bronchiolar tissue as compared with their controls. The induction of AP-1 activity by asbestos appeared to be mediated through the activation of mitogen-activated protein kinase family members, including extracellular signal-regulating protein kinase, Erk1 and Erk2. Aspirin inhibited asbestos-induced AP-1 activity in JB6 cells. Pretreatment of the mice with aspirin also inhibited asbestos-induced AP-1 activation in bronchiolar tissue. The data suggest that further investigation of the role of AP-1 activation in asbestos-induced cell proliferation and carcinogenesis is warranted. In addition, investigation of the potential therapeutic benefits of aspirin in the prevention/amelioration of asbestos-induced cancer is justified. (+info)
Review article: anthranoid laxatives and their potential carcinogenic effects.
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Anthranoid laxatives are widely used laxatives of natural origin. Because of their chemical structure they are carried unabsorbed to the large bowel, where metabolism to the active aglycones takes place. These aglycones exert their laxative effect by damaging epithelial cells, which leads directly and indirectly to changes in absorption, secretion and motility. Damaged epithelial cells can be found as apoptotic bodies in the pigmented colonic mucosa, characteristic for pseudomelanosis coli. Pseudomelanosis coli is a condition caused by chronic (ab)use of anthranoid laxatives and has recently been associated with an increased risk of colorectal carcinoma. In vitro and animal studies have shown a potential role of anthranoid laxatives in both the initiation and promotion of tumorigenesis. Studies in humans have also suggested tumour promoting activities for these laxatives. Although the short-term use of these substances is generally safe, long-term use cannot be recommended. (+info)