摘要:

Prostatic cancer is a common and frequently lethal malignant disease. In the United States and other countries the incidence and mortality rate of prostate cancer continue to rise. Cancer of the prostate has an extremely complex etiology and appears dependent on a variety of factors, making linkage to a single factor very difficult to detect. Cadmium is a metallic toxin of great environmental and occupational concern. Cadmium exposure has been associated with human prostatic cancer in some, but not all, epidemiologic studies. Some studies indicate that tissue levels of cadmium in the human prostate correlate with malignant disease. Any association between cadmium and prostatic cancer has been controversial, in large part because of a previous lack of relevant animal models. However, several chronic studies in rats revealing a correlation between cadmium exposure and pro‐static tumors have been published over the last several years. These include a study of oral cadmium exposure, a route extremely relevant to human exposure. Several of these chronic studies indicate a hormonal dependence of cadmium‐induced prostate cancer. Other supportive work continues to accumulate, such as studies showing in vitro malignant transformation of prostatic epithelial cells with cadmium exposure. In addition, there are indications that the primary biologic tolerance system for cadmium (i.e., the metallothionein gene) may be only poorly active in the specific lobes of the rat prostate in which cadmium induces tumors. The induction in rats of prostate cancer by cadmium treatment clearly supports, but does not definitively establish, a possible role for cadmium as an etiological agent in human prostate cancer. Further research, however, will be required to establish the precise role of cadmium in this important human malignancy.

ISSN:0098-4108    

DOI:10.1080/15287399409531920

出版商:Taylor & Francis Group    

年代:1994

数据来源: Taylor

摘要:

Organophosphorus compounds have been utilized as pesticides for almost five decades. They continue to be used as insecticides, helminthicides, ascaricides, nematocides, and to a lesser degree as fungicides and herbicides. While they have been and continue to be extremely useful in agricultural pest control throughout the world, their extensive use has led to numerous poisonings of nontarget species, including many human fatalities. The primary acute mammalian toxicity associated with exposure to organophosphorus pesticides results from inhibition of the enzyme acetylcholinesterase. However, other toxicities, some of which are life‐threatening but not related to acetylcholinesterase inhibition, have been observed following exposure to certain organophosphorus compounds. The focus of the current review is to summarize the known effects, both cholinergic and noncholinergic, of organophosphorus pesticides in mammals. Included in this summary is a discussion of the metabolic activation of organophosphorus pesticides, since this process plays a critical role in mediating the acute toxicities of many of these pesticides.

ISSN:0098-4108    

DOI:10.1080/15287399409531921

出版商:Taylor & Francis Group    

年代:1994

数据来源: Taylor

摘要:

The objective of this investigation was to determine the distribution of cholinergic (acetyl‐cholinesterase, AChE) and noncholinergic markers in slow‐, fast‐, and mixed‐fiber containing muscles (soleus, SOL; extensor digitorum longus, EDL; and diaphragm, DIA, respectively). Noncholinergic markers included high‐energy phosphates (adenosine triphosphate, ATP; phosphocreatine, PCr; and their metabolites), and the activity of creatine kinase (CK) and lactate dehydrogenase (LDH) and their isoenzymes and subforms. All three types of muscles had only one CK isoenzyme, CK‐MM, which totally consisted of MM3 subform. Levels of these determinants were highest in EDL followed by DIA and least in SOL. Another objective was to determine alterations of these markers under the influence of acute carbofuran (1.5 mg/kg) or methyl parathion (MPTH, 5 mg/kg) toxicity. Rats receiving either insecticide showed cholinergic signs with maximal severity including muscle fasciculations and convulsions within 15–30 min that lasted for about 2 h. At 1 h postinsecticide injection, when AChE was maximally inhibited (81–96%), significant depletion of ATP and PCr was evident in muscles (DIA > SOL > EDL), and activities of CK‐MM and LDH were elevated in muscles and consequently in serum. Serum CK‐MM3 activity was markedly reduced with sequential increase in MM2 and MM1 subforms, probably due to induced higher carboxypeptidase activity. These findings suggested that (1) the differences in levels of biochemical constituents in muscles depend upon the fiber type, (2) anticholinesterase insecticide‐induced increased muscle activity produces characteristic changes in CK and LDH isoenzymes patterns, and (3) leakage of these enzymeslisoenzymes into serum is due to depletion of ATP and PCr, which are required to maintain the cell membrane permeability.

ISSN:0098-4108    

DOI:10.1080/15287399409531922

出版商:Taylor & Francis Group    

年代:1994

数据来源: Taylor

摘要:

Because groundwater contamination is an important environmental concern, we examined the hepatic and renal effects of repeated exposure to a mixture of 25 chemicals frequently found in groundwater near hazardous‐waste disposal sites and the effect of such exposure on carbon tetrachloride (CCI4) toxicity. Adult male F‐344 rats received ad libitum deionized water and feed (Ad Lib Water) or ad libitum 10% MIX (referring to 10% of a technically achievable stock mixture) and feed for 14 d. Because exposure to the 25‐chemical mixture via the drinking water resulted in decreased water and feed consumption, restricted deionized water and feed controls (Restricted Water) were included. On d 14, rats were gavaged with 0, 0.0375, 0.05, 0.075 or 0.15 ml CCI4/kg, and hepatic and renal toxicity assessed 24 h later. Little or no hepatic and renal toxicity was observed in rats exposed to 10% MIX alone. No hepatic or renal lesions occurred that could be attributed to 10% MIX a/one. Slight but statistically significant alterations, of uncertain biological significance, resulted from the water treatments: 10% MIX increased alanine aminotransferase, urea nitrogen (BUN), and BUN/creatinine ratio; Restricted Water increased 5'‐nucleotidase and decreased alkaline phosphatase. Relative kidney weight was increased by both 10% MIX and Restricted Water. CCI4resulted in significant dosage‐dependent hepatotoxicity in all three water treatment groups but had little or no effect on renal indicators of toxicity. Relative to Ad Lib Water, significantly greater hepatotoxicity occurred in both 10% MIX and Restricted Water rats. The response to CCl4in the Restricted Water rats was similar to that of 10% MIX rats, indicating that a substantial portion of the effect of 10% MIX on CCI4hepatotoxicity is due to decreased water and feed intake.

ISSN:0098-4108    

DOI:10.1080/15287399409531923

出版商:Taylor & Francis Group    

年代:1994

数据来源: Taylor

摘要:

In 81 healthy individuals (51 smokers and 30 nonsmokers) biological indicators of internal exposure to electrophiles derived from tobacco smoke through metabolism were evaluated. Subgroups of smokers have been established in relation to the amount and type of tobacco smoked. Acetylator and hydroxylator phenotypes have been used as biomarkers of genetically determined susceptibility to cancer development. Urinary concentrations of thioethers (UT) and mutagenicity, with S9 mix for microsomal activation (MI‐S9), were higher in smokers in relation to the level of tobacco consumption, but not to the type of tobacco. The “Slow acetylators‐rapid oxidizers” category was not significant from the “rapid acetylators‐rapid oxidizers” for values of UT and MI‐S9. Data suggest that the biomarkers of exposure used in this study lack the necessary specificity to ascertain genetically determined susceptibility to cancer induced by tobacco smoking.

ISSN:0098-4108    

DOI:10.1080/15287399409531924

出版商:Taylor & Francis Group    

年代:1994

数据来源: Taylor

摘要:

Recently potentiation of oxidative damage in rat red blood cells (rRBC) incubated with t‐butylhydroperoxide (BHP) in combination with bromotrichloromethane (BrCCI3) was demonstrated. The mechanism by which this combination (BrCCI3/BHP) potentiates the oxidative damage to rRBC was investigated in this study. When rRBC were incubated with 0.1 mM BHP, 0.5 mM BrCCI3, or the two combined, BrCCI3/BHP‐potentiated lipid peroxidation and hemolysis were further enhanced under anaerobic conditions. However, the potentiation of lipid peroxidation was abolished by heating or trypsin digestion of rRBC. Electron spin resonance (ESR) studies demonstrated an increase of alkoxyl radical induced by BrCCI3/BHP in rRBC, and this increase was abolished by heating or predigestion of hemolysates with trypsin. The inhibition of lipid peroxidation by diphenylamine (which reacts with alkoxyl radicals but not peroxyl radicals) suggests an important role of alkoxyl radicals. Overall, the present findings demonstrate that the increase in radical‐related oxidative damage, possibly mediated by proteinlike materials, may be at least partially responsible for the potentiation of damage to rRBC induced by BrCCI3/BHP, and perhaps by BrCCI3. Although the in vivo significance of these results remains to be investigated, it seems likely that halocarbon toxicity may be amplified by elevated levels of lipid peroxide in blood.

ISSN:0098-4108    

DOI:10.1080/15287399409531925

出版商:Taylor & Francis Group    

年代:1994

数据来源: Taylor

摘要:

Cytotoxicities of metal salts were determined in the intestinal epithelial cell line I‐407 in microwell culture plates over 43 h using the widely utilized and accepted neutral red uptake procedure. Rank order cytotoxicities induced by the metal salts (in terms of LC50 values) were found to be HgCI2(32 μM) > CdCI2(53 μM) > CuCI2(156 μM) > TI2SO4(377 μM) > Pb(NO3)2(1.99 mM). Combined administration of the two most toxic metals at their LC50's showed that their toxicities were not additive or synergistic. The role of glutathione in determining toxicity induced by the metal salts in these cells was assessed by inhibition of its synthesis. Buthionine sulfoximine pretreatment at 1 mM, which was not toxic to the cells, caused sustained reduction in cellular glutathione content (to 13.8% after 48 h) and increased toxicities induced by HgCI2(5.7‐fold) and CuCI2(1.44‐fold) as shown by reductions in the LC50 values. Toxicity induced by the other metals remained unaffected. Administration of glutathione with either HgCI2or CdCI2did not protect the cells against their toxicity, and in the case of cadmium its toxicity was exacerbated.N‐Acetylcysteine diminished toxicity induced by mercury but not cadmium.

ISSN:0098-4108    

DOI:10.1080/15287399409531926

出版商:Taylor & Francis Group    

年代:1994

数据来源: Taylor

摘要:

Di(2‐ethylhexyl)phthalate (DEHP) is a commonly used plasticizer. Human exposure has been documented, and therefore it is important to investigate the toxic potential of this compound. When DEHP was administered in vivo, it was found to be a developmental toxicant in rodents. The purpose of this investigation was to determine if DEHP was directly embryo‐toxic to rat embryos. Embryos were cultured for 44 h beginning on gestational d 10. Embryos were cultured in rat serum to which DEHP was added to attain final concentrations within the 0.01–2.0% range. DEHP decreased growth and development at all tested concentrations higher than 0.5%. These results suggest that the parent compound itself is able to alter normal embryonic growth and development; however the high embryotoxic concentrations are unlikely to be attained in vivo.

ISSN:0098-4108    

DOI:10.1080/15287399409531927

出版商:Taylor & Francis Group    

年代:1994

数据来源: Taylor

摘要:

Pure cultures of anaerobic intestinal bacteria and mixed fecal microflora from human, rat, mouse, and pig were screened for the ability to metabolize 7‐nitrobenz[a]anthracene (7‐NO2BA). Based on analysis by high‐performance liquid chromatography (HPLC) and by ultraviolet (UV), mass, and nuclear magnetic resonance (NMR) spectral techniques, the compounds were identified as 7‐aminobenz[a]anthracene (7‐NH2BA) and benz[a]anthracene 7, 12‐dione (dione). Identification of 7‐NH2BA as a metabolite of 7‐NO2BA indicates that the anaerobic intestinal bacteria are capable of reducing 7‐NO2BA to potentially bioactive intermediates. The reductive capacities of the mixed intestinal microflora were generally greater than those of pure cultures. Thus, metabolism of 7‐NO2BA in the intestinal tract may 6e underestimated if pure cultures are used as the sole method for evaluating the potential hazard.

ISSN:0098-4108    

DOI:10.1080/15287399409531928

出版商:Taylor & Francis Group    

年代:1994

数据来源: Taylor

摘要:

A PRACTICAL GUIDE TO HUMAN CANCER GENETICSByS. V. HodgsonandE. R. MaherCambridge University Press, Cambridge, UK, 1993, 240 pp.

ISSN:0098-4108    

DOI:10.1080/15287399409531929

出版商:Taylor & Francis Group    

年代:1994

数据来源: Taylor