摘要:

Microcystis aeruginosa produces toxic cyclic peptides called microcystins, potent hepatotoxins that have been implicated in tumor promotion in skin and liver. The model used in this investigation was the azoxymethane (AOM)-induced aberrant crypt focus (ACF) in the male C57Bl/6J mouse colon. Three intraperitoneal (ip) injections of 5 mg/ kg AOM were administered at 7-d intervals to mice; 19 d after the last AOM injection, drinking water containing Microcystis extract was commenced and continued for a further 212 d. The content of microcystins in the drinking water was determined by mouse bioassay, high-performance liquid chromatography (HPLC), capillary eletrophoresis, and protein phosphatase inhibition. The doses employed were 0, 382, and 693 µg/kg bodyweight/d at the midpoint of the trial. Following postmortem examination blood cells, serum enzymes and organ pathology were investigated. A significant microcystin dose-dependent increase in the area of aberrant crypt foci was observed. There was no marked increase in the number of crypts/colon. Two overt colonic tumors (~30 mm3) were seen in microcystin-treated mice, and one microscopic colonic tumor in an AOMalone-treated mouse. This investigation provides the first evidence for the stimulation of preneoplastic colon tumor growth by microcystin.

ISSN:1528-7394    

DOI:10.1080/00984100050131305

出版商:Informa UK Ltd    

年代:2000

数据来源: Taylor

摘要:

In this study it was of interest to evaluate the impact of nitric oxide (NO) modulation by administration of arginine/NAME, on oxidative stress in experimental colitis induced by 2,4,6-trinitrobenzenesulfonic acid. Arginine was used to increase NO levels while NAME lowered oxidant levels. Histopathological findings of colon revealed mucosal inflammation in all groups but significantly higher with arginine alone. The levels of NO and of thiobarbituric acid-reactive substances (TBARS, a marker of lipid peroxidation) were observed to be significantly higher in the arginine-administered group compared to glycine, and these levels were found to decrease on administration of NAME to both glycine- and L-arginine-administered groups. Glutathione peroxidase (GSH-Px) activity and glutathione (GSH) levels were significantly higher in arginine administered group compared to glycine. Significantly higher CuZn superoxide dismutase (CuZn-SOD) activity was observed in the L-arginine + L-NAME group compared to arginine. Data show that NO plays a role in oxidant damage found in experimental colitis and that the use of NAME may potentially inhibit injury.

ISSN:1528-7394    

DOI:10.1080/00984100050131314

出版商:Informa UK Ltd    

年代:2000

数据来源: Taylor

摘要:

Ultraviolet A (UVA) radiation produces serious damage to skin, especially to dermis, but its damage to epidermis and responsible mechanisms are not fully understood. Studies were thus undertaken to investigate the effects of UVA or reactive oxygen species (ROS) on lipid peroxidation, cell cycle, and apoptosis in primary cultured rat keratinocytes and to determine the possible protective effects of tea polyphenols (TPP). UVA or ROS increased the release of plasma enzyme lactate dehydrogenase (LDH), and increased lipid peroxidation production (malondialdehyde, MDA), but decreased the activity of glutathione peroxidase (GSH-Px), indicating that UVA or ROS were cytostatic and peroxidizing to keratinocytes. TPP stabilized and protected cell membranes from ROS or UVA by inhibiting the release of LDH, lowering MDA levels, and increasing GSH-Px activity. Flow cytometry (FCM) analysis revealed that UVA or ROS decreased the proliferative index (PI); hence the cell growth was blocked in the S/G2 phase, with an increase in the percentage of apoptosis in primary keratinocytes. TPP modified the UVA or ROS-induced changes in PI and apoptosis. TPP may be useful to protect keratinocytes from UVA irradiation. In summary, these data demonstrated that UVA damage to skin keratinocytes in vitro was similar to that for ROS and that TPP protects against UVA-induced cytotoxicity by inhibiting lipid peroxidation and apoptosis.

ISSN:1528-7394    

DOI:10.1080/00984100050131323

出版商:Informa UK Ltd    

年代:2000

数据来源: Taylor

摘要:

The dermal bioavailability of mercury ''aged'' in soil for 3 mo was compared to that of pure mercury (without soil) and to mercury in brief contact with soil (16 h). Studies were conducted in vitro with [203Hg]mercuric chloride on dermatomed male pig skin by flow-through diffusion cell methodology. Less than 0.5% of the initial mercury dose penetrated through skin into receptor fluid after each treatment. The majority of pure mercury became covalently bound to skin. However, a short contact time with either an Atsion (sandy) or Keyport (clay) soil significantly decreased the total penetration of mercury (sum of receptor fluid and skin) by 40%. After aging, a 95% reduction in total penetration was observed for the compound relative to chemical without soil. Both soils bind mercury more strongly with time, as evidenced by larger quantities of radioactivity in soil and smaller amounts in skin decontaminate after aging than in soil for 16 h. Decreased mercury bioavailability with aging indicates lower health risk and reduced need for soil cleanup.

ISSN:1528-7394    

DOI:10.1080/00984100050131332

出版商:Informa UK Ltd    

年代:2000

数据来源: Taylor

摘要:

The simple and sensitive in vitro MCF-7 human breast cancer cell proliferation assay was used to examine the proliferation abilities of two Chinese commercial polychlorinated biphenyl (PCB) mixtures made in the 1960s. Chinese PCB3and Chinese PCB5

ISSN:1528-7394    

DOI:10.1080/00984100050131341

出版商:Informa UK Ltd    

年代:2000

数据来源: Taylor

摘要:

The objective of this study was to predict and validate the theoretically possible, maximal impact of metabolic interactions on the blood concentration profile of each component in mixtures of volatile organic chemicals (VOCs) [dichloromethane (DCM), benzene (BEN), trichloroethylene (TCE), toluene (TOL), tetrachloroethylene (PER), ethylbenzene (EBZ), styrene (STY), as well as para, ortho-, and meta- xylene ( p -XYL, o -XYL, m -XYL)] in the rat. The methodology consisted of: (1) obtaining the validated, physiologically based toxicokinetic (PBTK) model for each of the mixture components from the literature, (2) substituting the Michaelis?Menten description of metabolism with an equation based on the hepatic extraction ratio ( E ) for simulating the maximal impact of metabolic interactions (i.e., by setting E to 0 or 1 for simulating maximal inhibition or induction, respectively), and (3) validating the PBTK model simulations by comparing the predicted boundaries of venous blood concentrations with the experimental data obtained following exposure to various mixtures of VOCs. All experimental venous blood concentration data for 9 of the 10 chemicals investigated in the present study (PER excepted) fell within the boundaries of the maximal impact of metabolic inhibition and induction predicted by the PBTK model. The modeling approach validated in this study represents a potentially useful tool for screening/identifying the chemicals for which metabolic interactions are likely to be important in the context of mixed exposures and mixture risk assessment.

ISSN:1528-7394    

DOI:10.1080/00984100050131350

出版商:Informa UK Ltd    

年代:2000

数据来源: Taylor