Dietary cooked navy beans and their fractions attenuate colon carcinogenesis in azoxymethane-induced ob/ob mice.

Based on the protective effects of cooked dry bean consumption in a human intervention study, we evaluated which fraction of cooked dry beans is responsible for its cancer-preventive effects. Cooked navy beans (whole beans), the insoluble fraction (bean residue) or soluble fraction of the 60% (vol:vol) ethanol extract of cooked navy beans (bean extract), or a modified AIN-93G diet (16.6% fat including 12.

Silicosis and lung cancer: a fifty-year perspective.

The development of our studies on silica carcinogenesis and its mechanisms is reviewed. Starting from an analysis of the cellular reactions to silica in the pathogenesis of silicosis in the rat, followed by an analysis of the carcinogenic response to silica in the lungs of rats (but not in mice and hamsters), we went on to develop cellular models for culture and neoplastic transformation of rat alveolar epithelial cells. We studied the binding of silica to DNA, the generation of reactive oxygen species and the DNA damage mediated by hydroxyl radicals, showing marked differences among silica samples of varying purity.

Altered expression of adhesion molecules and epithelial-mesenchymal transition in silica-induced rat lung carcinogenesis.

Loss of the epithelial phenotype and disruption of adhesion molecules is a hallmark in the epithelial-mesenchymal transition (EMT) reported in several types of cancer. Most of the studies about the relevance of adhesion and junction molecules in lung cancer have been performed using established tumors or in vitro models. The sequential molecular events leading to EMT during lung cancer progression are still not well understood.

Hyperplasia of alveolar neuroendocrine cells in rat lung carcinogenesis by silica with selective expression of proadrenomedullin-derived peptides and amidating enzymes.

Pulmonary neuroendocrine (NE) cells are found as clusters called neuroepithelial bodies (NEBs) or as single cells scattered in the respiratory epithelium. They express a variety of bioactive peptides, and they are thought to be the origin of NE lung tumors. Proadrenomedullin N-terminal 20 peptide (PAMP) is a peptide derived from the same precursor as adrenomedullin (AM).

Relationship between surface properties and cellular responses to crystalline silica: studies with heat-treated cristobalite.

A fibrogenic sample of cristobalite dust, CRIS (crystalline silica of mineral origin), was heated to 1300 degrees C (CRIS-1300) to relate induced physicochemical modifications to cytotoxicity. Heating did not affect dust micromorphology and crystallinity, except for limited sintering and decreased surface area of CRIS-1300. Thermal treatments deeply affected surface properties.

Respiratory tract carcinogenesis by mineral fibres and dusts: models and mechanisms.

Experimental pathology studies in respiratory carcinogenesis by mineral fibres and dusts are reviewed. Animal models, analogous to the corresponding human pathology, were developed for carcinogenesis by polycyclic aromatic hydrocarbons carried on mineral particles, by N-nitroso compounds, by asbestos fibres and by crystalline silica (quartz). Species and organ susceptibility factors determine marked differences in the carcinogenic response to silica in different species and target organs, suggesting possible pathogenetic mechanisms, such as the role of surface oxygen radicals and the induction of related enzymes.

Transforming growth factor beta expression and transformation of rat lung epithelial cells by crystalline silica (quartz).

Crystalline silica (quartz) induces silicosis and associated peripheral lung carcinomas in rats. The role and pattern of expression of transforming growth factor (TGF)-beta1/beta2 mRNA transcripts were investigated in the fetal rat lung epithelial cell line FRLE, its neoplastic transformants and derived tumors in athymic nude mice. FRLE cells, treated with 100 microgram/cm2 of quartz in serum-free medium, gave rise to phenotypically altered, tumorigenic cells.

Vanadium(IV)-mediated free radical generation and related 2'-deoxyguanosine hydroxylation and DNA damage.

Free radical generation, 2'-deoxyguanosine (dG) hydroxylation and DNA damage by vanadium(IV) reactions were investigated. Vanadium(IV) caused molecular oxygen dependent dG hydroxylation to form 8-hydroxyl-2'-deoxyguanosine (8-OHdG). During a 15 min incubation of 1.

The association of cancers of the larynx with cancers of the lung.

We report 77 cases of associated primary cancers of the larynx and lung that were managed at the Department of Otolaryngology, University of Padua, between 1980 and 1994. To our knowledge, this is the largest series reported in the literature to date. This association is not a chance finding, but presumably the result of common pathogenetic factors.

DNA strand breakage, thymine glycol production, and hydroxyl radical generation induced by different samples of crystalline silica in vitro.

Five preparations of alpha-quartz [Min-U-Sil 5 (MQZ), MQZ pretreated with hydrofluoric acid (HFMQZ), Chinese standard alpha-quartz (CSQZ), and two German samples, DQ-12 and F600] and two preparations of the crystalline silica polymorphs, cristobalite and tridymite, previously characterized for surface area and surface charge, were evaluated for their relative activities in the following assays: (i) in vitro assays of short duration (< or = 15 min) for oxygen consumption and for generation of hydroxyl radicals (measured by electron spin resonance spin trapping), and (ii) in vitro assays of longer duration for DNA strand breakage (measured using linear DNA as a detector molecule) and for production of the oxidized DNA base, thymine glycol (measured by gas chromatography-mass spectrometry). Marked differences among the samples were found for their levels of oxygen consumption and of hydroxyl radicals' generation. All samples caused increased formation of thymine glycol, with wide variations in activity among samples.

Antioxidant activity of tetrandrine and its inhibition of quartz-induced lipid peroxidation.

Tetrandrine is a benzylisoquinoline alkaloid that has been used in China as an antifibrotic drug to treat the lesions of silicosis. Its mechanism in the treatment of silicosis is unclear. Electron spin resonance (ESR) spin trapping was employed to investigate the antioxidant properties of tetrandrine.

Transforming growth factor beta1, ras and p53 in silica-induced fibrogenesis and carcinogenesis.

The pathogenesis of mesenchymal and epithelial lung reactions was studied after a single intratracheal instillation of quartz into rats. Relationships between transforming growth factor beta1 (TGF-beta1) and the ras and p53 genes were investigated in silicosis and associated lung cancer. Immunohistochemical reactivity to mature TGF-beta1 was localized intracellularly in fibroblasts and macrophages at the periphery of silicotic granulomas and in stroma adjacent to hyperplastic alveolar type II cells and extracellularly in connective tissue matrix adjacent to hyperplastic alveolar type II cells.

Direct interaction between crystalline silica and DNA - a proposed model for silica carcinogenesis.

Crystalline silica in aqueous buffer produced oxygen radicals that mediated in vitro DNA (deoxyribonucleic acid) strand breakage. The oxidized DNA base, thymine glycol, was also produced. The hydroxyl radical, responsible for most DNA damage, has a reaction distance of about 15 Angstroms, requiring close contact of silica with DNA.

Neoplastic transformation by quartz in the BALB/3T3/A31-1-1 cell line and the effects of associated minerals.

Quartz, the most common form of crystalline silica, was tested quantitatively for neoplastic transformation in the mouse embryo cell line, BALB/3T3/A31-1-1. Five quartz dust samples of respirable size [Min-U-Sil 5 (MQZ); hydrofluoric-acid-etched MQZ (HFMQZ); Chinese standard quartz (CSQZ); DQ12; and F600] all induced significant levels of neoplastic transformation, showing dose-dependent increases in the frequency of morphologically transformed foci at lower tested doses and a plateau level of response at higher doses. The plateau levels reached by the five tested samples did not differ substantially (maximum transformation frequencies per 10(5) cells ranging from 53.

DNA binding to crystalline silica characterized by Fourier-transform infrared spectroscopy.

The interaction of DNA with crystalline silica in buffered aqueous solutions at physiologic pH has been investigated by Fourier-transform infrared spectroscopy (FT-IR). In aqueous buffer, significant changes occur in the spectra of DNA and silica upon coincubation, suggesting that a DNA-silica complex forms as silica interacts with DNA. As compared to the spectrum of silica alone, the changes in the FT-IR spectrum of silica in the DNA-silica complex are consistent with an Si-O bond perturbation on the surface of the silica crystal.

Mechanisms of carcinogenesis by crystalline silica in relation to oxygen radicals.

The carcinogenic effects of crystalline silica in rat lungs were extensively demonstrated by many experimental long-term studies, showing a marked predominance for adenocarcinomas originating from alveolar type II cells and associated with areas of pulmonary fibrosis (silicosis). In contrast with its effects in rats, silica did not induce alveolar type II hyperplasia and lung tumors in mice and hamsters, pointing to a critical role for host factors. Using these animal models, we are investigating the role of cytokines and other cellular mediators on the proliferation of alveolar type II cells.

Silica radical-induced DNA damage and lipid peroxidation.

In recent years, more attention has been given to the mechanism of disease induction caused by the surface properties of minerals. In this respect, specific research needs to be focused on the biologic interactions of oxygen radicals generated by mineral particles resulting in cell injury and DNA damage leading to fibrogenesis and carcinogenesis. In this investigation, we used electron spin resonance (ESR) and spin trapping to study oxygen radical generation from aqueous suspensions of freshly fractured crystalline silica.

Generation of thiyl and ascorbyl radicals in the reaction of peroxynitrite with thiols and ascorbate at physiological pH.

Electron spin resonance (ESR) spin trapping was utilized to investigate the reaction of peroxynitrite with thiols and ascorbate at physiological pH. The spin trap used was 5,5-dimethyl-1-pyrroline N-oxide (DMPO). The reaction of peroxynitrite with DMPO generated 5,5-dimethylpyrrolidone-(2)-oxy-(1) (DMPOX).

Binding of the cationic dye, Janus green B, as a measure of the specific surface area of crystalline silica in aqueous suspension.

Twelve preparations of crystalline silica, with a wide range of particle sizes, were assayed by a new method, which measures surface adsorption of the cationic dye Janus green B to crystalline silica samples in a buffered aqueous suspension. The same samples were also assayed for total surface area by the Brunauer-Emmett-Teller (BET) method of surface adsorption of nitrogen gas. A strong linear correlation was found between the two methods of measurement (r = 0.