Journal of toxicology and environmental health最新文献

{"title":"Differential carcinogenicity of benzo[a]pyrene in male and female CD-1 mouse lung.","authors":"R Sharma,&nbsp;A K Haque,&nbsp;S Awasthi,&nbsp;S V Singh,&nbsp;J T Piper,&nbsp;Y C Awasthi","doi":"10.1080/00984109708984052","DOIUrl":"https://doi.org/10.1080/00984109708984052","url":null,"abstract":"<p><p>Benzo[a]pyrene (BaP) is known to induce tumors in lung, forestomach, and skin in experimental animals. Earlier studies have suggested that glutathione S-transferase pi (GST pi) is involved in the detoxification of the \"ultimate\" carcinogenic metabolite of BaP, 7 beta, 8 alpha-dihydroxy-9 alpha, 10 alpha-oxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE). The constitutive expression of GST pi in the liver of the male CD-1 mouse is higher than that of the female, and BHA has been shown to preferentially induce GST pi in the female as compared with the male mouse. The present studies were therefore designed to compare the susceptibility of male and female CD-1 mice to the carcinogenic effects of BaP and the protective effect of BHA. Results of these studies show that the female CD-1 mice are more susceptibile to the carcinogenic effect of BaP than the males and that the attenuation of BaP-induced carcinogenesis by BHA appears to be restricted only to the females.</p>","PeriodicalId":17524,"journal":{"name":"Journal of toxicology and environmental health","volume":"52 1","pages":"45-62"},"PeriodicalIF":0.0,"publicationDate":"1997-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/00984109708984052","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20211905","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Styrene-induced alterations in the respiratory tract of rats treated by inhalation or intraperitoneally.","authors":"T Coccini,&nbsp;C Fenoglio,&nbsp;R Nano,&nbsp;P De Piceis Polver,&nbsp;G Moscato,&nbsp;L Manzo","doi":"10.1080/00984109708984053","DOIUrl":"https://doi.org/10.1080/00984109708984053","url":null,"abstract":"<p><p>Although exposure to styrene occurs primarily via inhalation, the action of this agent on the respiratory tract has scarcely been investigated. This article describes morphological and biochemical changes occurring in the respiratory tract of rats after either inhalation of styrene vapors (300 ppm, 6 h/d, 5 d/wk, for 2 wk) or systemic (ip) treatment with 40 or 400 mg/kg styrene for 3 consecutive days. Electron microscopy analysis showed diffuse cell damage involving the tracheal, bronchiolar, and alveolar epithelium. In the tracheal epithelium, several cell types were affected. Ciliated cells presented vacuolation, detachment of cilia, blebbing of the apical cytoplasm, and compound cilia. Most secretory cells showed scant secretory granules and blebbings. Dense bodies and fibrillary inclusions were seen in intermediate and basal cells. Styrene also caused alterations of cytoplasmic components in type II pneumocytes and bronchiolar cells as well as thickness of the alveolar wall. These abnormalities were accompanied by depletion of glutathione (GSH) in the lung tissue. Pneumotoxic effects of systemic administration of styrene were dose dependent and tended to be more severe than those seen in the animals exposed for longer periods to styrene by inhalation. Metabolic activation of styrene and subsequent cell damage induced by the reactive metabolite styrene oxide may be involved in the sequence of events culminating in the toxic insult to the respiratory tract.</p>","PeriodicalId":17524,"journal":{"name":"Journal of toxicology and environmental health","volume":"52 1","pages":"63-77"},"PeriodicalIF":0.0,"publicationDate":"1997-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/00984109708984053","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20211906","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mutagenicity of scooter exhaust particulate matter.","authors":"W Zhou,&nbsp;S H Ye","doi":"10.1080/00984109708984051","DOIUrl":"https://doi.org/10.1080/00984109708984051","url":null,"abstract":"<p><p>By using the in vitro Ames Salmonella/microsomal assay and the in vivo mouse micronucleus assay, studies were performed to evaluate the genotoxicity of gasoline exhaust particulate matter generated from five different domestic and imported scooters. In the Ames assay, treatment of test strains TA98 and TA100 with solvent extracts of particulate matter from four of five scooter models caused an increase in the number of histidine-independent colonies over the background in TA98 without S9 mix. Positive results were also obtained from the micronucleus assay. The frequencies of bone marrow micronucleated polychromatic erythrocytes were significantly higher in the treated compared to the nontreated animals, and the increases in the frequencies were not significantly different among the five types of scooters. Analyses of chemical components showed that scooter exhaust particulate matter contained more than 100 different substances including polycyclic aromatic hydrocarbons.</p>","PeriodicalId":17524,"journal":{"name":"Journal of toxicology and environmental health","volume":"52 1","pages":"35-44"},"PeriodicalIF":0.0,"publicationDate":"1997-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/00984109708984051","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20211904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aflatoxins in the lungs of children with kwashiorkor and children with miscellaneous diseases in Nigeria.","authors":"O A Oyelami,&nbsp;S M Maxwell,&nbsp;K A Adelusola,&nbsp;T A Aladekoma,&nbsp;A O Oyelese","doi":"10.1080/00984109708984048","DOIUrl":"https://doi.org/10.1080/00984109708984048","url":null,"abstract":"<p><p>Autopsy lung specimens from 20 children with kwashiorkor and 20 with other miscellaneous diseases, at the Obafemi Awolowo Teaching Hospital complex, Ile-Ife, Nigeria, were analyzed for the presence of aflatoxin using high-performance liquid chromatography. Aflatoxins were detected in 18 children who died from kwashiorkor but only in 13 of those who died from miscellaneous diseases. Of the 10 children, 5 in each group, who died with pneumonia, all had detectable levels of aflatoxins in their lungs. The two children with congestive cardiac failure, one secondary to pneumonia and the other secondary to tuberculous pericarditis, had more than two detectable aflatoxins in their lungs. These findings demonstrate that Nigerian children are exposed to aflatoxins and that high levels can accumulate in lung tissue.</p>","PeriodicalId":17524,"journal":{"name":"Journal of toxicology and environmental health","volume":"51 6","pages":"623-8"},"PeriodicalIF":0.0,"publicationDate":"1997-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/00984109708984048","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20186599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of glutathione depletion on cadmium-induced metallothionein synthesis, cytotoxicity, and proto-oncogene expression in cultured rat myoblasts.","authors":"M Shimizu,&nbsp;J F Hochadel,&nbsp;M P Waalkes","doi":"10.1080/00984109708984047","DOIUrl":"https://doi.org/10.1080/00984109708984047","url":null,"abstract":"<p><p>Cadmium (Cd) is a highly toxic metal and a known carcinogen. Although the carcinogenic mechanism of action is unknown, Cd will induce transcriptional activation of c-myc and c-jun. We have previously found that the extent of Cd-induced oncogene expression is limited by the presence of cellular metallothionein (MT) in rat L6 myoblasts. Glutathione (GSH) is thought to play an important role in protection against Cd before the onset of MT synthesis. Thus, this study examined the effects of GSH depletion on Cd-induced MT synthesis, cytotoxicity, and proto-oncogene expression in rat L6 myoblasts after pretreatment with L-buthionine sulfoximine (BSO), a potent inhibitor of gamma-glutamyl-cysteine synthetase, which effectively depletes GSH. Exposure of L6 cells to BSO (5 or 25 microM) resulted in a dose-dependent decrease in cellular GSH levels. GSH depletion had no effect on Cd- or zinc-induced MT synthesis. Although the depletion of GSH was not itself cytotoxic in L6 cells, BSO pretreatment, particularly at the higher dose (25 microM), resulted in a dose-dependent increase in the sensitivity to Cd cytotoxicity, as assessed by a tetrazolium-based dye (MTT) assay. Low levels of Cd (1 microM) slightly increased the expression of both c-myc and c-jun as assessed by increases in gene-specific mRNA levels, in accordance with previous studies. GSH depletion (5 muM BSO) likewise caused an increase in expression of c-myc and c-jun. However, combined GSH depletion and Cd exposure decreased levels of c-myc and c-jun transcription well below control levels. These results suggest that increased cytotoxicity resulting from exposure to Cd after BSO depletion of cellular GSH abrogates the oncogene activation observed after either treatment alone. Thus proto-oncogene expression induced by Cd appears to be dependent on the absence of over Cd-induced cytotoxicity.</p>","PeriodicalId":17524,"journal":{"name":"Journal of toxicology and environmental health","volume":"51 6","pages":"609-21"},"PeriodicalIF":0.0,"publicationDate":"1997-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/00984109708984047","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20186598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potential biomarkers of benzene exposure.","authors":"A M Medeiros,&nbsp;M G Bird,&nbsp;G Witz","doi":"10.1080/00984109708984042","DOIUrl":"https://doi.org/10.1080/00984109708984042","url":null,"abstract":"<p><p>Biological markers or biomarkers of exposure are indicators for the evaluation of the internal dose of a xenobiotic. Biomarkers integrate exposure from all routes and sources. This review presents a short overview of potential biomarkers of benzene exposure currently under investigation, the methodology used for their determination, and experimental findings and their usefulness and specificity in assessing exposure to benzene. Potential biomarkers of benzene exposure are benzene, benzene metabolites, and adducts formed by reactive benzene metabolites with cellular constituents. The potential biomarkers of benzene exposure described in this review are: (1) benzene, the parent hydrocarbon; (2) ring-hydroxylated urinary metabolites, phenol, catechol, hydroquinone, and 1,2,4-trihydroxybenzene; (3) trans,trans-muconic acid, a urinary ring-opened metabolite; (4) N-acetyl-S-(2,5-dihydroxyphenyl)-L-cysteine, a urinary metabolite of benzene, phenol, and hydroquinone; (5) S-phenylmercapturic acid, a glutathione-derived adduct; (6) N7-phenylguanine, a DNA adduct; and (7) S-phenylcysteine and N-phenyl-valine, hemoglobin/protein-derived adducts.</p>","PeriodicalId":17524,"journal":{"name":"Journal of toxicology and environmental health","volume":"51 6","pages":"519-39"},"PeriodicalIF":0.0,"publicationDate":"1997-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/00984109708984042","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20186035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potentiation of organophosphorus compound-induced delayed neurotoxicity (OPIDN) in the central and peripheral nervous system of the adult hen: distribution of axonal lesions.","authors":"J C Randall,&nbsp;B L Yano,&nbsp;R J Richardson","doi":"10.1080/00984109708984045","DOIUrl":"https://doi.org/10.1080/00984109708984045","url":null,"abstract":"<p><p>Clinical manifestations of mild organophosphorus compound-induced delayed neurotoxicity (OPIDN) produced by diisopropylphosphorofluoridate (DFP) in adult hens are potentiated by posttreatment with phenylmethanesulfonyl fluoride (PMSF). The purpose of this study was to assess whether potentiation of mild OPIDN produces a pattern of axonal lesions in the central and peripheral nervous system similar to that seen in severe OPIDN. Groups of 6 hens each were given the following priming/challenge doses sc at 0 and 4 h, respectively: 0.20 ml/kg corn oil/0.50 ml/kg glycerol formal (GF) (control); 0.50 mg/kg DFP/GF (low-dose DFP); 0.50 mg/kg DFP/60 mg/kg PMSF (potentiated DFP); 60 mg/kg PMSF/GF (PMSF alone); 60 mg/kg PMSF/1.5 mg/kg DFP (protected DFP); and 1.5 mg/kg DFP/GF (high-dose DFP). Two hens from each group were used to assay brain neurotoxic esterase (NTE) 24 h after the challenge dose, and the remaining hens were scored for deficits in walking, standing, and perching ability on d 18. Three hens from each group were perfusion-fixed on d 22 and neural tissues were prepared for histologic evaluation. DFP and/or PMSF caused > 88% brain NTE inhibition in all treated groups, compared to control. Protected DFP yielded no clinical deficits and a distribution and frequency of axonal lesions similar to control. PMSF alone produced a small increase in the frequency of lesions in the cervical spinal cord and peripheral nerves compared to control. Low-dose DFP caused minimal ataxia and increased frequency of axonal lesions in dorsal and lateral cervical spinal cord, ventral lumbar spinal cord, and inferior cerebellar peduncles (ICP) compared to control. Potentiated DFP and high-dose DFP produced maximal ataxia and essentially identical increases in the frequency of lesions in dorsal and ventral thoracic spinal cord, lateral lumbar spinal cord, and peripheral nerves compared to low-dose DFP. The results indicate that PMSF potentiation of mild OPIDN induced in adult hens by low-dose DFP results in an overall pattern of axonal degeneration like that produced by a threefold higher dose of DFP alone, and support the hypothesis that potentiation causes an increase in the frequency of axonal lesions in central and peripheral loci normally affected by OPIDN.</p>","PeriodicalId":17524,"journal":{"name":"Journal of toxicology and environmental health","volume":"51 6","pages":"571-90"},"PeriodicalIF":0.0,"publicationDate":"1997-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/00984109708984045","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20186038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of vanadium upon polyl:C-induced responses in rat lung and alveolar macrophages.","authors":"M D Cohen,&nbsp;S Becker,&nbsp;R Devlin,&nbsp;R B Schlesinger,&nbsp;J T Zelikoff","doi":"10.1080/00984109708984046","DOIUrl":"https://doi.org/10.1080/00984109708984046","url":null,"abstract":"<p><p>Hosts exposed to vanadium (V) display a subsequent decrease in their resistance to infectious microorganisms. Our earlier studies with rats inhaling occupationally relevant levels of V (as, ammonium metavanadate, NH4VO3) indicated that several nascent/inducible functions of pulmonary macrophages (PAM) were reduced. In the present study, V-exposed rats were examined to determine whether some of the same effects might also occur in situ. Rats were exposed nose-only to air or 2 mg V/m3 (as NH4VO3) for 8 h/d for 4 d, followed, 24 h later, by intratracheal (it) instillation of polyinosinic:polycytidilic acid (polyl:C) or saline. Analysis of lavaged lung cells/fluids after polyl:C instillation indicated that total lavageable cell/neutrophil numbers and protein levels, while significantly elevated in both exposure groups (as well as in saline-treated V-exposed rats), were always greater in V-exposed hosts. Exposure to V also affected the inducible production of interleukin 6 (IL-6) and interferon gamma (IFN gamma), but apparently not that of tumor necrosis factor-alpha (TNF alpha) or IL-1. Although polyl:C induced significant increases in lavage fluid IL-6 and IFN gamma levels in both exposure groups, levels were greater in V-exposed rats. If calculated with respect to total lavaged protein, however, V-exposed rats produced significantly less cytokine. Following polyl:C instillation, there were no marked exposure-related differences in basal or stimulated superoxide anion production by pooled lavaged cells or PAM specifically. With V-exposed rats, pooled cells recovered 24 h after saline instillation displayed reduced production (in both cases) compared to the air control cells; PAM-specific production was affected only after stimulation. In both exposure groups, polyl:C caused decreased superoxide production in recovered cells. Though less apparent with pooled cells, there was a time post polyl:C instillation-dependent decrease in stimulated PAM-specific superoxide production; this effect was greater in PAM from V-exposed rats than in PAM from air controls. Phagocytic activity of PAM from rats in both exposure groups was significantly increased by polyl:C instillation, although total activity in cells obtained from V-exposed rats was always significantly lower compared to air control cells. Our results indicate that short-term, repeated inhalation of occupationally relevant levels of V by rats modulates pulmonary immunocompetence. Modified cytokine production and PAM functionality in response to biological response modifiers (such as lipopolysaccharide, IFN gamma, or polyl:C) may be, at least in part, responsible for the increases in bronchopulmonary disease in humans occupationally exposed to V.</p>","PeriodicalId":17524,"journal":{"name":"Journal of toxicology and environmental health","volume":"51 6","pages":"591-608"},"PeriodicalIF":0.0,"publicationDate":"1997-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/00984109708984046","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20186039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oxidation of erythrocyte protein and lipid, and hemolysis in rabbit red blood cells treated with benzo[a]pyrene or adriamycin.","authors":"S K Lee,&nbsp;B M Lee","doi":"10.1080/00984109708984044","DOIUrl":"https://doi.org/10.1080/00984109708984044","url":null,"abstract":"<p><p>A number of free-radical-generating carcinogens catalyze the oxidative modification of macromolecules. Malondialdehyde (MDA), carbonyl content, alanine formation, and hemolysis were used as biomarkers of oxidative stress, and were determined in rabbit erythrocytes treated in vitro with benzo[a]pyrene or adriamycin. MDA and carbonyl content were significantly increased in a concentration-dependent manner by carcinogens. Alanine formation was also increased in a concentration-dependent manner in rabbit erythrocytes treated with carcinogens. Hemolysis occurred in erythrocytes treated with benzo[a]pyrene (540 microM) or adriamycin (300 microM) between 4 and 8 h of incubation, respectively. The hemolysis pattern correlated with increases in MDA, carbonyl content, and alanine formation. These data indicate that lipid peroxidation as measured by MDA may be the most sensitive indicator for oxidative stress in erythrocytes. Hemolysis could thus be applicable to free-radical-induced cellular damage as an alternative biomarker of oxidative stress.</p>","PeriodicalId":17524,"journal":{"name":"Journal of toxicology and environmental health","volume":"51 6","pages":"557-69"},"PeriodicalIF":0.0,"publicationDate":"1997-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/00984109708984044","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20186037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oxidative defense enzyme activity and mRNA levels in lenses of diabetic rats.","authors":"P Khanna,&nbsp;L Wang,&nbsp;R J Perez-Polo,&nbsp;N H Ansari","doi":"10.1080/00984109708984043","DOIUrl":"https://doi.org/10.1080/00984109708984043","url":null,"abstract":"<p><p>This study examines the mRNA expression and enzyme activity of oxidative defense enzymes during the course of streptozotocin-induced hyperglycemic cataract development. Diabetes was produced in 5-wk-old male Sprague-Dawley rats by administering streptozotocin ip and mRNA expression and enzyme activity were monitored on d 4, 8, 12, 16, 20, 40, 60, and 80; concomitantly, the onset and progress of cataract was followed by digital image analysis. Peak enzyme activity and mRNA expression were attained between d 20 and 40. Although catalase and glutathione peroxidase maintained high levels of mRNA expression through d 60, induction of CuZu-superoxide dismutase was transient, with the activity and mRNA levels returning to baseline values by d 40. There was a pronounced increase in aldose reductase activity, which gradually declined to basal levels by d 60; however, the mRNA levels remained unaltered. Other changes included a progressive loss of lenticular transparency, which declined to 40% of control by d 80. The role of antioxidant defense enzymes and, more interestingly, aldose reductase in combating oxidative stress in diabetic cataractogenesis is discussed.</p>","PeriodicalId":17524,"journal":{"name":"Journal of toxicology and environmental health","volume":"51 6","pages":"541-55"},"PeriodicalIF":0.0,"publicationDate":"1997-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/00984109708984043","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20186036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}