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The authors have previously demonstrated heterogeneities in the inflammatory activities of urban air fine (PM2.5–0.2) and coarse (PM10–2.5) particulate samples collected from six European cities with contrasting air pollution situations. The same samples (10 mg/kg) were intratracheally instilled to healthy C57BL/6J mice either once or repeatedly on days 1, 3, and 6 of the study week. The lungs were lavaged 24 h after the single dose or after the last repeated dosing. In both size ranges, repeated dosing of particles increased the total cell number in bronchoalveolar lavage fluid (BALF) more than the respective single dose, whereas cytokine concentrations were lower after repeated dosing. The lactate dehydrogenase (LDH) responses increased up to 2-fold after repeated dosing of PM2.5–0.2 samples and up to 6-fold after repeated dosing of PM10–2.5 samples. PM10–2.5 samples evoked a more extensive interstitial inflammation in the mouse lungs. The constituents with major contributions to the inflammatory responses were oxidized organic compounds and transition metals in PM2.5–0.2 samples, Cu and soil minerals in PM10–2.5 samples, and Zn in both size ranges. In contrast, poor biomass and coal combustion were associated with elevated levels of polycyclic aromatic hydrocarbons (PAHs) and a consistent inhibitory effect on the inflammatory activity of PM2.5–0.2 samples. In conclusion, repeated intratracheal instillation of both fine and coarse particulate samples evoked enhanced pulmonary inflammation and cytotoxicity compared to single-dose administration. The sources and constituents of urban air particles responsible for these effects appear to be similar to those encountered in the authors’ previous single-dose study. [ABSTRACT FROM AUTHOR]

We investigated the dose and time dependency of inflammatory and cytotoxic responses to size-segregated urban air particulate samples in the mouse lung. Coarse (PM10-2.5), fine (PM2.5-0.2), and ultrafine (PM0.2) particles were collected in six European cities (Duisburg, Prague, Amsterdam, Helsinki, Barcelona, Athens) in selected seasons using a modified Harvard high-volume cascade impactor. Healthy C57Bl/6J mice were intratracheally exposed to the particulate samples in a 24-h dose-response study (1, 3, and 10 mg/kg) and in 4-, 12-, and 24-h time course studies (10 mg/kg). After the exposures, the lungs were lavaged and the bronchoalveolar lavage fluid (BALF) was assayed for indicators of inflammation and tissue damage: total cell number, cell differential, total protein, and lactate dehydrogenase (LDH) and cytokine (tumor necrosis alpha [TNF-α], interleukin-6 [IL-6], and keratinocyte-derived chemokine [KC]) concentrations. In general, PM10-2.5 samples had higher inflammatory activity than PM2.5-0.2 samples. PM0.2 samples showed negligible inflammatory activity. PM10-2.5 and PM2.5-0.2 samples caused large increases in BALF cytokine concentrations at 4 h, but not at 12 or 24 h, after exposure. The BALF total cell number and total protein concentrations increased significantly at 12 h for both the PM10-2.5 and PM2.5-0.2 samples, but only PM10-2.5 samples produced consistent, significant increases at 24 h after exposure. There was more heterogeneity in BALF cytokine and neutrophil cell number responses to PM2.5-0.2 samples than to PM10-2.5 samples between the sampling campaigns. Thus, particle size, sources, and atmospheric transformation processes affect the inflammatory activity and response duration of urban air particulate matter in the mouse lung. [ABSTRACT FROM AUTHOR]

Purpose: The effects of low-level radiofrequency radiation (RFR) on ultraviolet (UV)-induced skin tumorigenesis were evaluated in ornithine decarboxylase (ODC) and non-transgenic mice. Materials and methods: Transgenic female mice over-expressing the human ODC gene and their non-transgenic littermates (20 animals in the cage control group, and 45-49 animals in the other groups) were exposed for 52 weeks to UV radiation or a combination of UV radiation and pulsed RFR. The UV dose was 240 Jm[sup -2] (1.2 × human minimum erythemal dose) delivered three times a week. One group of animals was exposed to Digital Advanced Mobile Phone System (DAMPS)-type RFR, the other group to Global System for Mobile (GSM)-type RFR at a nominal average specific absorption rate of 0.5 Wkg[sup -1], 1.5 hday[sup -1], for 5 days a week. The skin was carefully palpated weekly for macroscopic tumours. Histopathological analyses of all skin lesions and of a specified dorsal skin area were performed on all animals. Results: UV exposure resulted in development of macroscopic skin tumours in 11.5 and 36.8% of non-transgenic and transgenic animals, respectively. The RFR exposures did not give a statistically significant effect on the development of skin tumours in either transgenic or non-transgenic animals, or in combined analysis, but tumour development appeared slightly accelerated especially in non-transgenic animals. No effects of RFR exposures were found on excretion of 6-hydroxymelatonin sulphate into urine or on polyamine levels in dorsal skin. Conclusion: RFR exposures did not significantly enhance skin tumourigenesis. However, the slightly accelerated tumour development may warrant further evaluation. [ABSTRACT FROM AUTHOR]

Acute effects on the upper and lower respiratory tract due to inhalation exposure to Stachybotrys chartarum (Sc) extract were investigated in mice. In addition, the capacity of the Sc exposure to activate immune system and cause inflammation in the respiratory tract was studied. The inhalation of Sc extract aerosols was observed to provoke sensory irritation in the airways of both naive and Sc-immunized mice. In contrast, exposure to aerosolized ovalbumin or phosphate buffered saline did not cause this effect. Exposure to Sc twice a week for 3 wk increased significantly the serum total immunoglobulin E (IgE) levels in BALB/c mice immunized with Sc as well as in nonimmunized mice. A slight presence of inflammatory cells was observed in the alveoli 3 days after the last exposure to Sc. In conclusion, Sc extract has the capacity to provoke sensory irritation in the murine airways and to activate the murine immune system. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the effects of 50Hz magnetic fields (MF) on the development of cancer induced by ionizing radiation. Materials and methods: A total of 150 female CBA/S mice were randomized into three equal groups at the age of 3–5 weeks. One of the groups served as a 'cage-control group'. The two other groups were exposed to ionizing radiation in the beginning of the study. One of these two groups was exposed 24 h per day, for 1.5 years, to a 50 Hz vertical MF, the intensity of which varied regularly between 1.3, 13 and 130μT. The other served as a control group and was sham-exposed to MF in similar, but unenergized, exposure racks. Body weights, clinical signs, and food and water consumption were recorded regularly. Haematological examination, and the histopathological analysis of all lesions and major tissues were performed on all animals. Results: MF exposure did not increase the incidence of any primary neoplasms. However, the incidence of basophilic liver foci, a probable pre-neoplastic change in liver, was increased. The incidence of hepatocellular adenomas was unchanged, whereas the incidence of hepatocellular carcinomas was slightly, but not statistically significantly, elevated. Conclusions: It is concluded that overall the results of this study do not support a role for MF as a tumour promoter. [ABSTRACT FROM AUTHOR]

Background: The expression of inducible nitric oxide synthase (iNOS) has been reported to be altered in a number of tumours, but its role in tumour biology is still unclear. Methods: iNOS was studied in a series of 157 colorectal carcinoma patients and its relation to tumour grade, stage, cell cycle regulators, cell proliferation as well as survival was assessed. Results: iNOS intensity was moderate or intense in 37% of the tumours. iNOS intensity and percentage of positive cells were higher in Dukes A and B tumours than in Dukes C and D tumours, and low iNOS expression intensity was related to high histological grade. iNOS expression correlated positively with cell cycle regulators p21 and AP-2. There was also a high iNOS expression intensity and high fraction of iNOS positive cells in tumours with a high amount of tumour infiltrating lymphocytes (TILs). The cancer related survival was significantly lower among patients with a low signal for iNOS and low iNOS percentage in tumour epithelium. In multivariate analysis iNOS was not an independent prognostic factor. Conclusions: These results suggest that iNOS has a protective role in colorectal carcinogenesis, but further studies are required to establish the clinical significance of iNOS in colorectal cancer. [ABSTRACT FROM AUTHOR]

Abstract. Purpose: To study the possible role of 50 Hz magnetic fields (MF) in UV-induced skin tumourigenesis using a sensitive animal model. Materials and methods: Transgenic mice (line K2) over-expressing the human ornithine decarboxylase ( ODC ) gene and their nontransgenic littermates were exposed for 10.5 months to UV-only or a combination of UV and a continuous (100 mu T) or an intermittent MF with varying intensity (1.3-130 mu T). Results: Both MF exposure and transgenicity enhanced the onset rate of macroscopically detectable tumours, but the effect was statistically significant only for the MF exposure ( p 0.015). The number of animals bearing malignant tumours was low and similar in all exposure groups. Epidermal cysts (EC) appeared to be strongly associated with both MF exposure and high ODC activity (transgenic animals). However, EC are not known to be associated with carcinogenesis. The UV-only or combined UV and MF exposure did not affect the ODC activities measured at the end of the exposure. Conclusions: These results support the proposed tumour-promoting effect of MF, but do not suggest an important role for increased ODC activity in this process. [ABSTRACT FROM AUTHOR]

Background: CD44 is a cell adhesion molecule often expressed in the form of various splice variants. The role of standard CD44 isoform (CD44s) and its variants in colorectal carcinogenesis is partly conflicting. Therefore, we compared the expression of CD44s (hermes-3) and its splice variants (v3 and v6) with traditional prognostic factors in 194 colorectal cancer patients treated at Kuopio University Hospital and followed up for a mean of 14 years. Methods: Formalin-fixed, paraffin-embedded tissue sections from 194 patients with colorectal carcinoma were examined immunohistochemically to detect the expression of different forms of CD44. The hypothesis that CD44s, CD44v3, and CD44v6 expression intensities and distribution in cancer cells correlated with survival was tested with the log-rank test, hazard ratios, and their confidence intervals. Results: In high-grade tumours CD44s and CD44v6 expression intensities and CD44s percentages were stronger than in low-grade tumours. CD44v6, CD44v3, and CD44s expression intensities in tumour epithelium were also stronger in Dukes C and D tumours than in A and B tumours. In the univariate survival analysis patients with strong CD44s, CD44v3, and CD44v6 expression intensities in tumour epithelium had lower cancer-related survival than the patients who had weak CD44s, CD44v3, and CD44v6 expression intensities. Recurrence-free survival was also shorter in patients with intense signals for CD44v3 and CD44v6 in tumour epithelium. In the multivariate analysis the CD44v6 expression intensity in tumour epithelium predicted independently both cancer-related and recurrence-free survival in T1-4N0-3M0 and T1-3N0M0 cases. In addition, the CD44v3 expression intensity in tumour epithelium was a significant predictor of RFS in T1-3N0M0 cases. Conclusions: These results strongly suggest that the CD44 splice variants v6 and v3 have prognostic significance in colorectal cancer. [ABSTRACT FROM AUTHOR]