RESUMEN
Relative intensities of singly-charged mono-bromide silver clusters Ag(x)Br(+) formed from sputtering of a pressed pellet of silver bromide were measured by mass spectrometry. The obtained results suggest that the Ag(x)Br(+) clusters have a structural formula of the form Ag(x-1)(+)(AgBr). The relative stability of Ag(x-1)(+)(AgBr) was determined by the intrinsic stability of the remaining metallic portion of the cluster (Ag(x-1)(+)) as predicted by the spherical jellium model (SJM). Unimolecular and high- energy collision-induced dissociation (CID) spectra of Ag(x)Br(+) (x = 2, 4, 6, 8, 10) clusters were also measured. In all of the spectra, the most intense fragment peaks were assigned to the Ag(x-1)(+) ions accompanying the loss of AgBr. The difference in the relative intensities of the Ag(x-1)(+) peaks between unimolecular dissociation and CID spectra led us to conclude that the weakest bond in the excited cluster Ag(x)Br(+*) is the Ag(x-1)(+)-AgBr bond and the structure of Ag(x)Br(+) is a metallic Ag(x-1)(+) ion cluster adduct with AgBr. The primary fragments observed in the CID spectra were also explained by the stabilities of the generated ion products and neutral fragments, both having even delocalized valence electrons. The present results were consistently explained by SJM. The dissociation behavior of Ag(2)Br(+) can be explained on the basis of the calculated thermochemical data.
RESUMEN
The present study was designed to evaluate whether gestational exposure to an EMF targeting the head region, similar to that from cellular phones, might affect embryogenesis in rats. A 1.95-GHz wide-band code division multiple access (W-CDMA) signal, which is one applied for the International Mobile Telecommunication 2000 (IMT-2000) system and used for the freedom of mobile multimedia access (FOMA), was employed for exposure to the heads of four groups of pregnant CD(SD) IGS rats (20 per group) for gestational days 7-17. The exposure was performed for 90 min/day in the morning. The spatial average specific absorption rate (SAR) for individual brains was designed to be 0.67 and 2.0 W/kg with peak brain SARs of 3.1 and 7.0 W/kg for low (group 3) and high (group 4) exposures, respectively, and a whole-body average SAR less than 0.4 W/kg so as not to cause thermal effects due to temperature elevation. Control and sham exposure groups were also included. At gestational day 20, all dams were killed and fetuses were taken out by cesarean section. There were no differences in maternal body weight gain. No adverse effects of EMF exposure were observed on any reproductive and embryotoxic parameters such as number of live (243-271 fetuses), dead or resorbed embryos, placental weights, sex ratios, weights or external, visceral or skeletal abnormalities of live fetuses.
Asunto(s)
Encéfalo/efectos de la radiación , Teléfono Celular , Campos Electromagnéticos/efectos adversos , Embrión de Mamíferos/efectos de la radiación , Exposición Materna , Animales , Anomalías Congénitas/etiología , Exposición a Riesgos Ambientales , Femenino , Embarazo , Preñez/efectos de la radiación , Ratas , Ratas Sprague-DawleyRESUMEN
Doubly protonated phosphopeptide (YGGMHRQET(p)VDC) ions obtained by electrospray ionization were collided with Xe and Cs targets to give singly and doubly charged positive ions via collision-induced dissociation (CID). The resulting ions were analyzed and detected by using an electrostatic analyzer (ESA). Whereas doubly charged fragment ions resulting from collisionally activated dissociation (CAD) were dominant in the CID spectrum with the Xe target, singly charged fragment ions resulting from electron transfer dissociation (ETD) were dominant in the CID spectrum with the Cs target. The most intense peak resulting from ETD was estimated to be associated with the charge-reduced ion with H2 lost from the precursor. Five c-type fragment ions with amino acid residues detached consecutively from the C-terminal were clearly observed without a loss of the phosphate group. These ions must be formed by N--Calpha bond cleavage, in a manner similar to the cases of electron capture dissociation (ECD) and ETD from negative ions. Although the accuracy in m/z of the CID spectra was about +/-1 Th because of the mass analysis using the ESA, it is supposed from the m/z values of the c-type ions that these ions were accompanied by the loss of a hydrogen atom. Four z-type (or y--NH3, or y--H2O) ions analogously detached consecutively from the N-terminal were also observed. The fragmentation processes took place within the time scale of 4.5 micros in the high-energy collision. The present results demonstrated that high-energy ETD with the alkali metal target allowed determination of the position of phosphorylation and the amino acid sequence of post-translational peptides.
Asunto(s)
Álcalis/química , Metales/química , Fosfopéptidos/análisis , Fosfopéptidos/química , Espectrometría de Masa por Ionización de Electrospray/métodos , Transporte de Electrón , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Electricidad EstáticaRESUMEN
The modifying potential of diacylglycerol (DAG) oil on tumor development was investigated in a medium-term multi-organ carcinogenesis bioassay. DAG oil is a cooking oil that contains >80% diglycerides, <20% triglycerides and <5% monoglycerides. Male 6-week-old F344 rats (20 in each group) were sequentially treated with five carcinogens for initiation in different organ target sites for 4 weeks (DMBDD treatment), and then administered DAG oil at dietary levels of 0% (control), 1.375%, 2.75% or 5.5% [triacylglycerol (TGs), with the same fatty acid composition as DAG oil were also added at dietary levels of 5.5%, 4.125%, 2.75% and 0%, respectively, to maintain the same lipid level], or 5.5% high linoleic acid TG (HLTG), 5.5% high oleic acid TG (HOTG), or 5.5% medium-chain TG (MCTG) (as reference substances, mostly consisting of triacylglycerols) admixed into AIN-93G semi-synthetic diet, for an additional 24 weeks. Controls received standard diet without any supplementation as non-treated control. All animals were killed at the end of week 28, and the major organs were carefully examined for preneoplastic and neoplastic lesions. No DAG oil treatment-related changes were noted in survival, general conditions, body weights, food consumption and organ weights. Upon quantitative analysis of glutathione S-transferase placental form (GST-P) positive foci of the liver, DAG oil was not found to exert any effects. The incidence of colon adenomas was significantly increased in rats given 1.375% DAG oil, but not 2.75% and 5.5% DAG oil, when compared to the control (5.5% TG group) value. Furthermore, incidences and multiplicity of hyperplasias and adenomas and/or adenocarcinomas were comparable across all DAG oil-treated groups. In contrast, incidences of colon adenomas and/or adenocarcinomas were significantly increased in rats given 5.5% HOTG, and adenomas with MCTG, but not 5.5% HLTG, as compared to the 5.5% TG value. Preneoplastic and neoplastic lesions induced by DMBDD treatment in various organs other than the large intestine were comparable in all cases. Thus, the current results indicate that DAG oil may not exert modifying potential on tumor development, even in the colon because of the lack of dose-dependence. DAG oil was equivalent to HOTG (standard cocking oil composed of naturally occurring fatty acids), with regard to colon tumor development. Further dose-response study concerning HOTG may be needed to confirm whether the enhancing effect of large intestine carcinogenesis exert or not.
Asunto(s)
Pruebas de Carcinogenicidad , Carcinógenos/toxicidad , Diglicéridos/toxicidad , Neoplasias/inducido químicamente , Animales , Peso Corporal/efectos de los fármacos , Neoplasias del Colon/inducido químicamente , Neoplasias del Colon/patología , Dieta , Ingestión de Líquidos/efectos de los fármacos , Interacciones Farmacológicas , Ingestión de Alimentos/efectos de los fármacos , Glutatión Transferasa/metabolismo , Masculino , Neoplasias/patología , Tamaño de los Órganos/efectos de los fármacos , Ratas , Ratas Endogámicas F344 , Análisis de Supervivencia , Triglicéridos/análisisRESUMEN
A subchronic oral toxicity study of purple corn color (PCC), a natural food colorant, was performed with groups of 10 male and 10 female F344 rats fed the agent at dietary levels of 0%, 0.5%, 1.5% and 5.0% for 90 days. No mortalities occurred during the treatment period. No treatment-related changes in the body weight, food and water consumption, ophthalmology, hematology, organ weight data and histopathology were observed. Regarding general conditions and gross pathology, staining of fur and black feces were noted in rats of the 1.5% and 5.0% diet groups. Moreover, brown urine and black material in the stomach, small and large intestine were evident in rats receiving 5.0%. These changes were considered due to the anthocyanin content. On clinical chemistry analysis, total cholesterol, phospholipid and triglyceride were significantly lowered in both sexes of the 5.0% group, but these were not considered to be toxicologically significant. Thus, the No-observed-adverse-effect-level (NOAEL) was judged to be 5.0% in diet for both sexes (male: 3542 mg/kg/day, female: 3849 mg/kg/day) for PCC under the present experimental conditions.
Asunto(s)
Antocianinas/toxicidad , Dieta , Colorantes de Alimentos/toxicidad , Animales , Antocianinas/metabolismo , Relación Dosis-Respuesta a Droga , Femenino , Colorantes de Alimentos/metabolismo , Masculino , Nivel sin Efectos Adversos Observados , Tamaño de los Órganos/efectos de los fármacos , Ratas , Ratas Endogámicas F344 , SeguridadRESUMEN
The present study was performed to evaluate effects of a 2-year exposure to an electromagnetic near-field (EMF) equivalent to that generated by cellular phones on tumor development in the central nervous system (CNS) of rats. For this purpose, pregnant F344 rats were given a single administration of N-ethylnitrosourea (ENU) on gestational day 18. A total of 500 pups were divided into five groups, each composed of 50 males and 50 females: Group 1, untreated controls; Group 2, ENU alone; Groups 3 to 5, ENU + EMF (sham exposure and two exposure levels). A 1.95-GHz wide-band code division multiple access (W-CDMA) signal, which is a feature of the International Mobile Telecommunication 2000 (IMT-2000) cellular system was employed for exposure of the rat head starting from 5 weeks of age, 90 min a day, 5 days a week, for 104 weeks. Brain average specific absorption rates (SARs) were designed to be .67 and 2.0 W/kg for low and high exposures, respectively. The incidence and numbers of brain tumors in female rats exposed to 1.95-GHz W-CDMA signals showed tendencies to increase but without statistical significance. Overall, no significant increase in incidences or numbers, either in the males or females, was detected in the EMF-exposed groups. In addition, no clear changes in tumor types in the brain were evident. Thus, under the present experimental conditions, exposure of heads of rats to 1.95-GHz W-CDMA signals for IMT-2000 for a 2-year period was not demonstrated to accelerate or otherwise affect ENU-initiated brain tumorigenesis.
Asunto(s)
Neoplasias Encefálicas/etiología , Neoplasias Encefálicas/patología , Teléfono Celular , Campos Electromagnéticos , Neoplasias Inducidas por Radiación/etiología , Neoplasias Inducidas por Radiación/patología , Animales , Relación Dosis-Respuesta a Droga , Relación Dosis-Respuesta en la Radiación , Exposición a Riesgos Ambientales , Etilnitrosourea , Femenino , Masculino , Dosis de Radiación , Ratas , Ratas Endogámicas F344RESUMEN
Chronic toxicity and carcinogenicity of hinokitiol (beta-thujaplicin), used as an antibiotic and fungicidal agent of a food additive, was examined in both sexes of F344/DuCrj (F344) rats. In this chronic toxicity study, groups of 10 rats of each sex were given a diet containing hinokitiol at doses of 0, 0.005, 0.015 and 0.05% for 52 weeks. No treatment-related adverse effects were noted in the survival rate, general condition, body weights, food consumption, urinalysis, hematology and clinical chemistry. Slight but significant elevation of spleen and liver weights was noted in both sexes given 0.05% hinokitiol, along with an increase in hemosiderin deposits in male spleens, related to chelator binding of iron, together with slight centrilobular hypertrophy of male hepatocytes. However, these alterations were negligible and not toxicologically significant. In the carcinogenicity study, groups of 50 female and 50 male rats were given a diet containing hinokitiol at doses of 0, 0.005, 0.015 and 0.05% (excluding 0.005% in females). No treatment-related changes in survival rate, general condition, body weight, food consumption, hematology and organ weights were noted. Detailed histopathological examination revealed no treatment-related increase in the incidences of any neoplastic lesions. The results demonstrate that hinokitiol is not carcinogenic in F344 rats of either sex.
Asunto(s)
Aditivos Alimentarios/toxicidad , Monoterpenos/toxicidad , Neoplasias Experimentales/inducido químicamente , Tropolona/análogos & derivados , Animales , Peso Corporal/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Femenino , Masculino , Ratas , Ratas Endogámicas F344 , Tropolona/toxicidadRESUMEN
F344 male rats were given five consecutive weekly subcutaneous injections of folic acid for induction of chronic renal dysfunction and then di(2-ethylhexyl)phthalate (DEHP) or di(2-ethylhexyl)adipate (DEHA) in the diet at a concentration of 0, 6000 or 25,000 ppm for 4 weeks in order to investigate whether male reproductive toxicity of the two chemicals might be enhanced under conditions of renal disease. Control animals also received DEHP or DEHA in the same manner but without folic acid pretreatment. Decreased testicular weights, seminiferous atrophy with vacuolization of sertoli cells and diminished sperm counts were more prominent in rats given folic acid and then 25,000 ppm DEHP as compared to those exposed to DEHP alone. No such reproductive toxicity was evident in rats given 6000 ppm DEHP or either dose of DEHA. An increased concentration of the mono-derivative of DEHP (mono(2-ethylhexyl)phthalate, MEHP) in the blood, testis and urine was considered relevant to the enhanced reproductive toxicity observed with DEHP.
Asunto(s)
Adipatos/toxicidad , Dietilhexil Ftalato/análogos & derivados , Genitales Masculinos/efectos de los fármacos , Enfermedades Renales/metabolismo , Riñón/efectos de los fármacos , Plastificantes/toxicidad , Adipatos/farmacocinética , Animales , Peso Corporal/efectos de los fármacos , Dietilhexil Ftalato/farmacocinética , Dietilhexil Ftalato/toxicidad , Relación Dosis-Respuesta a Droga , Epidídimo/efectos de los fármacos , Ácido Fólico , Genitales Masculinos/metabolismo , Genitales Masculinos/patología , Riñón/metabolismo , Riñón/patología , Enfermedades Renales/inducido químicamente , Enfermedades Renales/patología , Masculino , Plastificantes/farmacocinética , Próstata/efectos de los fármacos , Ratas , Ratas Endogámicas F344 , Vesículas Seminales/efectos de los fármacos , Espermatogénesis/efectos de los fármacos , Testículo/efectos de los fármacosRESUMEN
Doubly charged tungsten hexacarbonyl W(CO)(6) (2+) ions were made to collide with Ar and K targets to give singly and doubly charged positive ions by collision-induced dissociation (CID). The resulting ions were analyzed and detected by using a spherical electrostatic analyzer. Whereas the doubly charged fragment ions resulting from collisional activation (CA) were dominant with the Ar target, singly charged fragment ions resulting from electron transfer were dominant with the K target. The internal energy deposition in collisionally activated dissociation (CAD) evaluated with the Ar target was broad and decreased with increasing internal energy. The predominant peaks observed with the K target were associated with singly charged W(CO)(2) (+) and W(CO)(3) (+) ions: these ions were not the result of CA, but arose from dissociation induced by electron transfer (DIET). The internal energy deposition resulting from the electron transfer was very narrow and centered at a particular energy, 7.8 eV below the energy level of the W(CO)(6) (2+) ion. This narrow internal energy distribution was explained in terms of electron transfer by Landau-Zener potential crossing at a separation of 5.9 x 10(-8) cm between a W(CO)(6) (2+) ion and a K atom, and the coulombic repulsion between singly charged ions in the exit channel. A large cross section of 1.1 x 10(-14) cm(2) was estimated for electron capture of the doubly charged W(CO)(6) (2+) ion from the alkali metal target, whose ionization energy is very low. The term "collision-induced dissociation," taken literally, includes all dissociation processes induced by collision, and therefore encompasses both CAD and DIET processes in the present work. Although the terms CID and CAD have been defined similarly, we would like to propose that they should not be used interchangeably, on the basis that there are differences in the observed ions and in their intensities with Ar and K targets.
RESUMEN
There is increasing evidence that dose-response curve of genotoxic carcinogen is nonlinear and a practical threshold dose exists. However, little is known about differences in the dose-response relationship of genotoxic carcinogen among different strain rats. Herein, we showed that low doses of genotoxic carcinogen 2-amino-3,8-dimethylimidazo[4,5-f] quinoxaline (MeIQx) had no effects on induction of liver glutathione S-transferase placental form (GST-P)-positive foci in both BN and F344 rats, and therefore demonstrated the existence of no-observed effect level for hepatocarcinogenicity of this genotoxic carcinogen irrespective of strains. These findings further support our notion that a practical threshold dose for MeIQx hepatocarcinogenicity exists in rats.
Asunto(s)
Carcinógenos/toxicidad , Gutatión-S-Transferasa pi/metabolismo , Neoplasias Hepáticas Experimentales/inducido químicamente , Hígado/efectos de los fármacos , Lesiones Precancerosas/inducido químicamente , Quinoxalinas/toxicidad , Animales , Hígado/enzimología , Hígado/patología , Neoplasias Hepáticas Experimentales/enzimología , Masculino , Nivel sin Efectos Adversos Observados , Lesiones Precancerosas/enzimología , Ratas , Ratas Endogámicas BN , Ratas Endogámicas F344RESUMEN
The carcinogenic potential of silicone resin (KS66), used as an antifoaming food additive, was examined in both sexes of F344 rats. Groups of 50 female and 50 male animals were given diet containing KS66 at doses of 0%, 1.25% and 5.0%. No treatment related effects were noted regarding survival rate, general condition, body weight, food consumption, hematology and organ weight data. Detailed histopathological examination revealed no treatment-related increase in the incidences of any non-neoplastic or neoplastic lesions. The results demonstrate that KS66 is not carcinogenic in F344 rats of either sex.
Asunto(s)
Carcinógenos , Aditivos Alimentarios/toxicidad , Animales , Conducta Animal/efectos de los fármacos , Peso Corporal/efectos de los fármacos , Pruebas de Carcinogenicidad , Dieta , Ingestión de Alimentos/efectos de los fármacos , Femenino , Masculino , Neoplasias/inducido químicamente , Neoplasias/epidemiología , Tamaño de los Órganos/efectos de los fármacos , Ratas , Ratas Endogámicas F344 , Siliconas , Análisis de SupervivenciaRESUMEN
N-nitrosocompounds, which induce cancers in various organs, may be formed endogenously with intake of amino compounds such as secondary amines and sodium nitrite (NaNO(2)) in combination. The present study was performed to investigate whether three amino compounds, 1-methyl-9H-pyrido[3,4-b]indole (harman), 9H-pyrido[3,4-b]indole (norharman) and 2-amino-1,3,4-triazole (amitrole), might be converted in vivo to compounds capable of promoting hepatocarcinogenesis when given with NaNO(2). However, in an 8-week model, no modifying potential was evident in terms of numbers and areas of putative preneoplastic glutathione S-transferase placental form (GST-P)-positive foci in any of the groups receiving paired treatments. These results demonstrate that combinations of harman, norharman and amitrole with NaNO(2) lack promoting effects for liver carcinogenesis in our medium-term bioassay system.
Asunto(s)
Amitrol (Herbicida)/toxicidad , Harmina/análogos & derivados , Harmina/toxicidad , Neoplasias Hepáticas Experimentales/inducido químicamente , Nitrito de Sodio/toxicidad , Animales , Carbolinas , Masculino , Ratas , Ratas Endogámicas F344 , Aumento de Peso/efectos de los fármacosRESUMEN
The present study was designed to evaluate whether a 2 year exposure to an electromagnetic field (EMF) equivalent to that generated by cellular phones can accelerate tumor development in the central nervous system (CNS) of rats. Brain tumorigenesis was initiated by an intrauterine exposure to N-ethylnitrosourea (ENU) on gestational day 18. A total of 500 pups were divided into five groups, each composed of 50 males and 50 females: Group 1, untreated control; Group 2, ENU alone; Groups 3-5, ENU + EMF (sham exposure and 2 exposure levels). A 1.439 GHz time division multiple access (TDMA) signal for the Personal Digital Cellular (PDC), Japanese standard cellular system was used for the exposure of the rat head starting from 5 weeks of age, 90 min a day, 5 days a week, for 104 weeks. Brain average specific absorption rate (SAR) was 0.67 and 2.0 W/kg for low and high exposures, respectively: whole body average SAR was less than 0.4 W/kg. There were no inter-group differences in body weights, food consumption, and survival rates. No increase in the incidences or numbers per group of brain and/or spinal cord tumors, either in the males or females, was detected in the EMF exposed groups. In addition, no clear changes in tumor types were evident. Thus, under the present experimental conditions, 1.439 GHz EMF exposure to the heads of rats for a 2 year period was not demonstrated to accelerate or affect ENU initiated brain tumorigenesis.
Asunto(s)
Teléfono Celular , Neoplasias del Sistema Nervioso Central/etiología , Exposición a Riesgos Ambientales/efectos adversos , Microondas/efectos adversos , Neoplasias Inducidas por Radiación/etiología , Medición de Riesgo/métodos , Neoplasias del Sistema Nervioso Central/patología , Relación Dosis-Respuesta en la Radiación , Incidencia , Neoplasias Inducidas por Radiación/patología , Dosis de Radiación , Factores de Riesgo , Factores Sexuales , Análisis de SupervivenciaRESUMEN
Humans may be exposed to 2-amino-3,8-dimethylimidazo[4,5-f ]quinoxaline (MeIQx) at low doses during the period of gestation and lactation, and thereafter throughout life. The current study was designed to examine the possibility that early exposure may increase the risk of liver tumor development and related genetic changes. Male and female F344 rats were therefore administered MeIQx in diet (1, 10 and 100 ppm) for 4 weeks before mating and also during gestation and lactation. We also examined the carcinogenic risk of low-dose maternal and post-weaning exposure (MeIQx at doses of 1 and 10 ppm). Surviving male F1 rats were sacrificed under ether anesthesia at 19 weeks of age for analyses of glutathione S-transferase placental form-positive foci in the liver and aberrant crypt foci in the colon, as putative preneoplastic lesions. Transplacental and trans-breast milk exposure to MeIQx did not enhance development of the lesions, and levels of cell proliferation in the liver also did not differ from control values. However, excretion of MeIQx into breast milk and transfer to the fetus and offspring were observed with resultant hepatic MeIQx-DNA adducts and 8-hydroxy-2'-deoxyguanosine formation. Thus, our data suggest that maternal exposure to MeIQx during the period of pregnancy and lactation may not increase the risk of hepatocarcinogenesis in male offspring, despite causing genetic damage. If this result can be extrapolated to humans, exposure to MeIQx may not increase carcinogenic risk in offspring at usual human exposure levels.
Asunto(s)
Carcinógenos/toxicidad , Colon/efectos de los fármacos , Aductos de ADN/biosíntesis , Desoxiguanosina/análogos & derivados , Desoxiguanosina/metabolismo , Hígado/efectos de los fármacos , Lesiones Precancerosas/inducido químicamente , Quinoxalinas/toxicidad , 8-Hidroxi-2'-Desoxicoguanosina , Animales , Carcinógenos/metabolismo , Proliferación Celular , Colon/enzimología , Colon/patología , Neoplasias del Colon/inducido químicamente , Neoplasias del Colon/enzimología , Dieta , Femenino , Glutatión Transferasa/metabolismo , Humanos , Lactancia , Hígado/enzimología , Hígado/patología , Neoplasias Hepáticas Experimentales/inducido químicamente , Neoplasias Hepáticas Experimentales/enzimología , Masculino , Leche Humana/efectos de los fármacos , Leche Humana/enzimología , Placenta/efectos de los fármacos , Placenta/enzimología , Lesiones Precancerosas/enzimología , Embarazo , Quinoxalinas/metabolismo , Ratas , Ratas Endogámicas F344RESUMEN
Reproductive effects have been observed in experimental animals treated with di(n-butyl)phthalate (DBP), one of phthalate esters used in soft plastics and a variety of consumer products. In this study, we investigated whether testicular toxicity of DBP is influenced by diminished renal function. To generate an experimental condition reflecting chronic renal disease in man, adult male F344 rats were given five consecutive weekly subcutaneous injections of folic acid at a dose of 300 mg/kg and then a diet containing 1200, 5000, and 20,000 ppm of DBP for 4 weeks. These concentrations roughly correspond to 60, 250, and 1000 mg/kg per day per rat, respectively. Folic acid clearly induced interstitial nephritis accompanied by impairment of renal function. Seminiferous degeneration, diminished spermatogenesis and increase in the number of morphologically abnormal sperm were more prominent in rats given folic acid and then 20,000 ppm DBP as compared to those exposed to DBP alone. These data suggest that DBP-induced male reproductive toxicity can be increased by folic acid-induced renal dysfunction.
Asunto(s)
Dibutil Ftalato/toxicidad , Ácido Fólico/toxicidad , Riñón/efectos de los fármacos , Testículo/efectos de los fármacos , Animales , Peso Corporal/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Epidídimo/efectos de los fármacos , Epidídimo/patología , Riñón/patología , Masculino , Tamaño de los Órganos/efectos de los fármacos , Ratas , Ratas Endogámicas F344 , Testículo/patologíaRESUMEN
We investigated changes of gene expression in livers of rats treated with carcinogens and tumor promoters using a novel three-dimensional microarray system developed by Olympus Optical Co., Ltd., to assess the feasibility of predicting modifying effects on hepatocarcinogenesis on the basis of changes in the patterns. For this purpose, two genotoxic carcinogens, two nongenotoxic carcinogens (promoters) and seven candidate chemopreventive agents were examined. Six-week-old male F344 rats were treated for 2 weeks with the 11 chemicals (0.05% phenobarbital, 0.3% clofibrate, 0.01% N-diethylnitrosamine (DEN), 0.01% 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 1% catechol, 1% caffeic acid, 0.05% nobiletin, 0.05% garcinol, 0.05% auraptene, 0.05% zermbone and 0.05% 1'-acetoxychavicol acetate (ACA). Test chemicals were mixed in food with the exception of DEN, which was administered in drinking water. RNAs from liver were then analyzed using two kinds of customized microarrays (PamChip(\xa8) microarray A spotted for 28 genes of drug-metabolizing enzymes in duplicate, and PamChip microarray B spotted for 131 genes which are known to be up- or down-regulated in hepatocarcinoma cells). Hybridization and subsequent analysis were usually completed within 2 h and the data obtained were highly reproducible. Carcinogens were classified into genotoxic and nongenotoxic substances by clustering analysis. We could also divide test chemicals into carcinogens and chemopreventive agents from their effects on gene expression. In this study, we have thus shown that it is feasible to predict the modifying effects of chemicals on the basis of changes of gene expression patterns after only 2 weeks of exposure, using our novel three-dimensional microarrays.
Asunto(s)
Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Neoplasias Hepáticas/genética , Análisis de Secuencia por Matrices de Oligonucleótidos/métodos , Animales , Anticarcinógenos/farmacología , Carcinógenos/farmacología , Hibridación in Situ , Neoplasias Hepáticas/inducido químicamente , Masculino , ARN Mensajero/análisis , Ratas , Reproducibilidad de los Resultados , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
A mass spectrograph using a position sensitive detector was designed and constructed. It has an image contractor lens system and a zoom lens system. The position sensitive detector consists of a micro channel plate (MCP) and a charge-coupled device (CCD). The performance of this new instrument was tested with methylstearate as a sample.
Asunto(s)
Cromatografía de Gases y Espectrometría de Masas/instrumentación , Cromatografía de Gases y Espectrometría de Masas/métodos , Glándulas Endocrinas , Estudios de Evaluación como Asunto , Tecnología de Fibra Óptica , Xenobióticos/análisisRESUMEN
The current study was designed to examine the modulating effects of bisphenol A (BPA) on prostate cancer risk in male offspring exposed transplacentally and lactationally. BPA was administered to F344 female rats by gavage at 0, 0.05, 7.5, 30, 120 mg/kg/day during pregnancy and lactation periods. When F1 males reached 5 weeks old, they were given 10 subcutaneous injections of 3,2'-dimethyl-4-aminobiphenyl (DMAB) or corn oil vehicle and rats were then sacrificed under ether anesthesia at week 60. There were no observable effects on the accessory sex organ weights of male offspring. Transplacental and lactational exposure to BPA did not affect the incidences of preneoplastic and neoplastic lesions in the accessory sex organs (prostate and seminal vesicle) of F1 rats and did not induce any proliferating lesions without DMAB. Our data suggest that maternal exposure to BPA during the period of pregnancy and lactation does not affect the risk of prostate carcinogenesis in male offspring.
Asunto(s)
Estrógenos no Esteroides/toxicidad , Intercambio Materno-Fetal , Fenoles/toxicidad , Efectos Tardíos de la Exposición Prenatal , Próstata/efectos de los fármacos , Administración Oral , Compuestos de Aminobifenilo/toxicidad , Animales , Compuestos de Bencidrilo , Peso Corporal/efectos de los fármacos , Pruebas de Carcinogenicidad , Carcinógenos/toxicidad , Relación Dosis-Respuesta a Droga , Interacciones Farmacológicas , Estrógenos no Esteroides/administración & dosificación , Femenino , Lactancia , Masculino , Exposición Materna , Fenoles/administración & dosificación , Embarazo , Próstata/patología , Neoplasias de la Próstata/inducido químicamente , Neoplasias de la Próstata/patología , Ratas , Ratas Endogámicas F344 , Vesículas Seminales/efectos de los fármacos , Vesículas Seminales/patologíaRESUMEN
This study was designed to evaluate and characterize any subacute toxicity of 1-carboxy-5,7-dibromo-6-hydroxy-2,3,4-trichloroxanthone (HXCA), an impurity of Phloxine B (Food Red No. 104 in Japan, D&C Red No. 28 in the USA), when administered to both sexes of F344 rats at dietary levels of 0 (control), 0.005, 0.05 and 0.5%. During the study, the treatment had no effects on clinical signs, survival, urinalysis or ophthalmology. Hematology, blood biochemistry, gross pathology, organ weights, organ to body weight ratios and histopathology exhibited no differences of toxicological significance between control and treated rats. Reactions to treatment may be summarized as follows: there was a tendency for increased food and water consumption and decreased food efficiency in both sexes of the 0.5% group. Thus, these results indicated the no-observed-adverse-effect level (NOAEL) of HXCA to be 0.05% (39.3 mg/kg/day for males, and 41.0 mg/kg/day for females).
Asunto(s)
Eosina I Azulada/toxicidad , Colorantes de Alimentos/toxicidad , Xantonas/toxicidad , Animales , Seguridad de Productos para el Consumidor , Dieta , Relación Dosis-Respuesta a Droga , Ingestión de Líquidos/efectos de los fármacos , Contaminación de Medicamentos , Ingestión de Alimentos/efectos de los fármacos , Eosina I Azulada/química , Femenino , Concentración de Iones de Hidrógeno , Masculino , Nivel sin Efectos Adversos Observados , Ratas , Ratas Endogámicas F344 , Factores de Tiempo , Pruebas de Toxicidad , Orina/química , Xantonas/química , Xantonas/metabolismoRESUMEN
The potential of purple sweet potato color (PSPC) and red cabbage color (RCC), natural anthocyanin food colors, to modify colorectal carcinogenesis was investigated in male F344/DuCrj rats, initially treated with 1,2-dimethylhydrazine (DMH) and receiving 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in the diet. After DMH initiation, PSPC and RCC were given at a dietary level of 5.0% in combination with 0.02% PhIP until week 36. No PSPC or RCC-treatment-related changes in clinical signs and body weight were found. Incidences and multiplicities of colorectal adenomas and carcinomas in rats initiated with DMH were clearly increased by PhIP. In contrast, lesion development was suppressed by RCC, or tended to be inhibited by PSPC administration. Furthermore, in the non-DMH initiation groups, induction of aberrant crypt foci (ACF) by PhIP was significantly decreased by RCC supplementation. The results thus demonstrate that while PhIP clearly exerts promoting effects on DMH-induced colorectal carcinogenesis, these can be reduced by 5.0% PSPC or 5.0% RCC in a diet under the present experimental conditions.