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1.
Curr Issues Mol Biol ; 44(11): 5221-5233, 2022 Oct 26.
Artículo en Inglés | MEDLINE | ID: mdl-36354667

RESUMEN

The superoxide dismutase (SOD) is the principal antioxidant defense system in the body that is activated by a reactive oxygen species. Some variants of the SOD2 gene have been associated with cancer. The rs4880 variant was determined by PCR real-time and the rs5746136 variant by PCR-RFLP in healthy subjects and in breast cancer (BC) patients. The rs4880 and rs5746136 variants were associated with BC susceptibility when BC patients and the control group were compared for the CT, TT, CTCC, and the T alleles (p < 0.05). The CT genotype of the rs4880 variant showed significant statistical differences in patients and controls aged ≤ 45 years old, and with hormonal consumption (p < 0.05). The rs4880 variant was associated with BC patients with CTTT genotype and obesity, the presence of DM2-SAH, and a non-chemotherapy response (p < 0.05). Additionally, the rs5746136 variant was associated with susceptibility to BC with Ki-67 (≥20%), luminal A type BC, and a chemotherapy partial response (p < 0.05) in BC patients who carry TT, TC, and CTTT genotypes, respectively. The haplotype T/T (OR 1.98; 95% CI 1.20−3.26, p = 0.005) was observed to be a risk factor for BC. The rs4880 and rs5746136 variants in the SOD2 gene were associated with BC susceptibility.

2.
Environ Mol Mutagen ; 62(3): 177-184, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33496960

RESUMEN

Most women with breast cancer can become pregnant and give birth while undergoing radiation therapy and breastfeeding is generally not contraindicated. The induction of long-lived reactive species in proteins, such as casein by X-ray radiation and DNA damage to unexposed organisms, has been shown when ingesting irradiated cheese. To determine whether exposing lactating rats to X-rays increases the number of micronucleated erythrocytes (MNEs) in peripheral blood of their unexposed or breastfeeding rat pups, 15 female Wistar rats were divided into three groups: Negative control; Experimental group exposed to X-rays, and group exposed to X-rays plus vitamin C. The mothers of groups 2 and 3 were irradiated for three consecutive days after giving birth, returning them to their respective cages each time to continue lactation. A blood sample was taken from the mothers and pups at 0, 24, and 48 hr. Blood smears were stained with acridine orange to analyze MNEs. In mother rats, the frequency of micronucleated polychromatic erythrocytes (MNPCEs) increased significantly at 24 and 48 hr in both study groups exposed to radiation. Likewise, in rat pups the MNPCE and MNE frequencies increased in both groups with radiation and radiation plus vitamin C at 24 and 48 hr, and a protection from vitamin C was observed. In conclusion, the genotoxic damage produced in rat pups that were lactated by mothers irradiated with X-rays is possibly due to the effect of long-lived reactive species that were formed in the breast milk of female Wistar rats during the irradiation process.


Asunto(s)
Daño del ADN/genética , Eritrocitos/efectos de la radiación , Lactancia/efectos de la radiación , Micronúcleos con Defecto Cromosómico/efectos de la radiación , Animales , Neoplasias de la Mama/complicaciones , Neoplasias de la Mama/radioterapia , Daño del ADN/efectos de la radiación , Eritrocitos/patología , Femenino , Lactancia/genética , Masculino , Pruebas de Micronúcleos , Madres , Embarazo , Ratas , Ratas Wistar , Rayos X/efectos adversos
3.
Am J Med Genet C Semin Med Genet ; 184(4): 1023-1029, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-33274538

RESUMEN

Mutations in three genes (APP, PSEN1, and PSEN2) are the main cause of the autosomal dominant early-onset Alzheimer's disease (AD-EOAD). In PSEN1, the A431E (c.1292C>A, rs63750083) mutation is suspected to have exerted a founder effect in the State of Jalisco, Mexico. In Guadalajara, Jalisco, Mexico, this mutation was found in 46 index cases evaluated for AD-EOAD. In our genealogical analysis, 301 affected relatives of the mutation carriers were identified, 195 of whom were already deceased at the time of interview. Moreover, 560 descendants had a 50% risk of carrying the mutation, and 348 were potentially at risk. A systematic phenotyping was performed in 39 patients. The mean onset age was 42.5 ± 3.9 years, and no significant difference in onset age was observed between the male and female patients. Furthermore, a substantial clinical heterogeneity and high frequencies of spastic paraparesis, language disorders, and neuropsychiatric symptoms were observed. To our knowledge, the investigated families represent the second biggest population carrying a PSEN1 mutation in Latin America, offering a unique opportunity to study the genetic basis of Alzheimer's disease. Addressing AD-EOAD warrants an integral approach involving a deep understanding of its clinical behavior, as well as counseling protocols and prevention studies.


Asunto(s)
Enfermedad de Alzheimer , Precursor de Proteína beta-Amiloide , Adulto , Edad de Inicio , Enfermedad de Alzheimer/genética , Precursor de Proteína beta-Amiloide/genética , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mutación , Presenilina-1/genética
4.
Ann Clin Lab Sci ; 48(2): 152-157, 2018 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-29678840

RESUMEN

The aim of the study was to determine if amniotic fluid cells of rats can be used to provide evidence of genotoxicity. In order to do that micronuclei formation was induced in rats during pregnancy after treatment with cyclophosphamide (CP), at different CP doses. On gestational day 19, we collected the amniotic fluid and determined the frequency of micronucleated cells (MNCs) from the offspring. Samples were centrifuged and placed on clean slides. The smears were observed with an epifluorescence microscope. The number of MNCs in 2000 cells per pregnant rat was counted. The fetus weight and size were recorded and provided evidence of DNA damage caused by CP administration to their mothers. A significantly greater number of MNCs was observed only for the medium CP dose (P<0.01) and the high CP dose (P<0.02) groups versus the negative control group. Birth defects produced by the administration of the CP were evident in the CP-treated groups. This study showed an alternative method to determine if compounds administrated to pregnant rat cause damage to the genetic material of their offspring. Using micronuclei testing of amniotic fluid cells enables us to determine in one test the genotoxicity and the teratogenic potential of a compound.


Asunto(s)
Líquido Amniótico/efectos de los fármacos , Ciclofosfamida/toxicidad , Inmunosupresores/toxicidad , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Efectos Tardíos de la Exposición Prenatal/patología , Animales , Animales Recién Nacidos , Ciclofosfamida/farmacología , Daño del ADN/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Femenino , Pruebas de Micronúcleos , Embarazo , Lesiones Prenatales/inducido químicamente , Ratas , Ratas Wistar , Estadísticas no Paramétricas
5.
J Med Food ; 20(2): 197-199, 2017 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-28005446

RESUMEN

This study was performed to investigate the effect of Agave tequilana Weber inulin on postprandial ghrelin levels in obese patients. A randomized, double-blind, cross-over design was performed. A total of 14 patients were allocated into two groups: one group received a drink that contained 500 mL lemon water, 24 g of A. tequilana Weber inulin, and 75 g glucose and the other group received a placebo drink with 500 mL lemon drink and 75 g of glucose. After a 7-day washout period, the groups were crossed. The primary outcome measure was postprandial ghrelin levels between minute 240 and minute 270. A. tequilana Weber inulin did not change postprandial ghrelin concentration in obese patients.


Asunto(s)
Agave/química , Ghrelina/sangre , Inulina/administración & dosificación , Obesidad/tratamiento farmacológico , Extractos Vegetales/administración & dosificación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Obesidad/sangre , Periodo Posprandial , Resultado del Tratamiento
6.
J Photochem Photobiol B ; 165: 141-146, 2016 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-27792890

RESUMEN

Exposure to ultraviolet-A (UVA) light can accidentally cause adverse effects in the skin and eyes. UVA induces DNA damage directly by creating pyrimidine dimers or by the formation of reactive oxygen species that can indirectly affect DNA integrity. UVA radiation is emitted by lamps from everyday devices. In adult rats, micronucleated erythrocytes (MNE) are removed from the circulation by the spleen. However, in newborn rats, MNE have been observed in peripheral blood erythrocytes. The objective of this study was to use micronucleus tests to evaluate the DNA damage caused in newborn rats exposed to UVA light from three different types of UVA lamps obtained from commonly used devices: counterfeit detectors, insecticide devices, and equipment used to harden resins for artificial nails. Rat neonates were exposed to UVA lamps for 20min daily for 6days. The neonates were sampled every third day, and the numbers of MNE and micronucleated polychromatic erythrocytes (MNPCE) in the peripheral blood were determined. The rat neonates exposed to the three types of UVA lamps showed increased numbers of MNE and MNPCE from 48h to 144h (P<0.05 and P<0.001 respectively). However, no relationship was observed between the number of MNE and the wattage of the lamps. In conclusion, under these conditions, UVA light exposure induced an increase in MNE without causing any apparent damage to the skin.


Asunto(s)
Núcleo Celular/efectos de la radiación , Eritrocitos/efectos de la radiación , Rayos Ultravioleta , Animales , Animales Recién Nacidos , Pruebas de Micronúcleos , Ratas
7.
Genet Test Mol Biomarkers ; 20(8): 438-44, 2016 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-27228364

RESUMEN

AIM: The aim of this study was to investigate the association of the rs2240308 and rs1133683 polymorphisms in the AXIN2 gene with colorectal cancer (CRC) in Mexican patients. MATERIALS AND METHODS: Genomic DNAs from 201 CRC patients and 100 healthy blood donors were analyzed for AXIN2 gene polymorphisms by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology. Statistical associations were calculated using the odds ratio (OR) test. RESULTS: The genotype distribution of the rs1133683 polymorphism C > T showed a statistical difference between the two study groups (p = 0.0019). Moreover, OR analyses demonstrated that individuals with either the C/T or T/T genotype have a decreased risk for CRC compared with individuals with the C/C genotype (OR = 0.47, 95% confidence interval [CI] = 0.25-0.86, p = 0.0134 and OR = 0.24, 95% CI = 0.10-0.57, p = 0.005, respectively). This association was also evident in a stratified analysis based on tumor-node-metastasis (TNM) stage. For the rs2240308 polymorphism C > T, the OR analysis showed a significantly increased risk for carriers of the T/T genotype (OR = 2.64, 95% CI = 1.12-6.24, p = 0.0236) and this association was also evident in the stratified analysis by TNM stage. CONCLUSION: Our results indicate the possibility that variations in the AXIN2 gene may play a significant role in promoting or preventing CRC development.


Asunto(s)
Proteína Axina/genética , Neoplasias Colorrectales/genética , Adenocarcinoma/epidemiología , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Adulto , Alelos , Proteína Axina/metabolismo , Estudios de Casos y Controles , Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales/metabolismo , Femenino , Frecuencia de los Genes , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Humanos , Masculino , México/epidemiología , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Regiones Promotoras Genéticas
9.
Artículo en Inglés | MEDLINE | ID: mdl-25868130

RESUMEN

Pregnant hairless rat dams were exposed to ultraviolet-A light (UVA) to induce micronucleated erythrocytes (MNE) in their fetuses. The control group was exposed to conventional light; the experimental groups were exposed to UVA (365nm) during gestational days 16-21. In some cases, ascorbic acid (Asc) was administered in the drinking water from gestational day 15 until delivery. Dams were sampled at 48-h intervals during gestation, from day 16 until delivery. Blood was also obtained from neonates at birth; MNE, micronucleated polychromatic erythrocytes (MNPCE), and polychromatic erythrocytes (PCE) were scored. Increased MNE and MNPCE were observed in neonates born to mothers exposed to UVA for 40, 80 or 160min, compared to the control group. Asc treatment reduced MNE and MNPCE induction.


Asunto(s)
Eritrocitos/efectos de la radiación , Micronúcleos con Defecto Cromosómico/efectos de la radiación , Efectos Tardíos de la Exposición Prenatal/genética , Rayos Ultravioleta , Animales , Animales Recién Nacidos , Antioxidantes/farmacología , Ácido Ascórbico/farmacología , Eritrocitos/efectos de los fármacos , Eritrocitos/metabolismo , Femenino , Masculino , Micronúcleos con Defecto Cromosómico/efectos de los fármacos , Pruebas de Micronúcleos , Embarazo , Efectos Tardíos de la Exposición Prenatal/prevención & control , Ratas sin Pelo , Factores de Tiempo
10.
J Photochem Photobiol B ; 141: 283-7, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-25463679

RESUMEN

In previous studies, exposure to phototherapy, but not oxygen therapy, resulted in damage to genetic material in newborns. The objective of this study was to determine whether micronucleated erythrocytes (MNE) increased in preterm newborns (PNBs) who were exposed to blue light phototherapy lamps. MNE of mature organisms are rapidly eliminated by the spleen, and the presence of MNE has been related to immaturity in some species. Furthermore, PNBs present spontaneous MNE. Blood samples were taken from 17 PNBs at birth to establish baseline frequencies (0 h). After beginning blue light phototherapy, blood samples were obtained from 11 of these PNBs at 24-h intervals for 96 h, after the baseline sample. MNE and micronucleated polychromatic erythrocytes (MNPCE) were counted. The basal values of MNE and MNPCE from 17 PNBs were 0.62 ± 0.48 and 1.52 ± 1.28 (‰), respectively, and no increase in MNE or MNPCE was observed in the serial samples of 11 PNBs exposed to blue light and oxygen therapies, though previous studies reported increases using other types of lamps. In conclusion, under the conditions described no increase in the number of MNE or MNPCE was observed in the peripheral blood of PNBs exposed to blue light phototherapy.


Asunto(s)
ADN/metabolismo , Luz , ADN/química , Eritrocitos/citología , Eritrocitos/efectos de la radiación , Femenino , Edad Gestacional , Humanos , Oxigenoterapia Hiperbárica , Hiperbilirrubinemia/terapia , Recién Nacido , Recien Nacido Prematuro , Masculino , Fototerapia
11.
Folia Neuropathol ; 52(1): 22-9, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24729340

RESUMEN

Genetic variants that confer susceptibility to Parkinson's disease (PD) show unbalanced distribution among different populations; genetic predisposition to either familial or sporadic forms of PD in Mexican-mestizo population has not been comprehensively studied. The aim of the present study was to analyze genetic variants in six PARK genes in PD patients. In total 381 individuals (173 patients, 208 controls) were genotyped for p.Gly2019Ser and p.Gly2385Arg variants of LRRK2. The p.Gly2019Ser variant was present in two patients and one healthy control; the p.Gly2385Arg variant was not found. In a subgroup of early-onset PD (EOPD), MLPA analysis was done for PARKIN (PARK2), PINK1 (PARK6), DJ-1 (PARK7), LRRK2 (PARK8), SNCA (PARK1/4) and ATP13A2 (PARK9). We found a heterozygous deletion of exon 2 in PARK2 in the youngest patient of the early-onset group, who showed limited response to antiparkinsonian therapy. Although the changes Gly2019Ser and Gly2385Arg of LRRK2 are associated with PD in different populations; they may be a rare cause of PD in our population. Novel population-specific variants may underlie PD susceptibility in Mexican mestizos. Our study suggests that the heterozygous deletion of exon 2 in the PARK2 gene is a risk factor for EOPD.


Asunto(s)
Enfermedad de Parkinson/genética , Proteínas Serina-Treonina Quinasas/genética , Ubiquitina-Proteína Ligasas/genética , Anciano , Estudios Transversales , Análisis Mutacional de ADN , Femenino , Predisposición Genética a la Enfermedad/genética , Variación Genética , Genotipo , Humanos , Proteína 2 Quinasa Serina-Treonina Rica en Repeticiones de Leucina , Masculino , México/epidemiología , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa Multiplex , Enfermedad de Parkinson/epidemiología , Prevalencia , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa
12.
Asia Pac J Clin Nutr ; 21(2): 312-8, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22507620

RESUMEN

Some studies, that consider polymorphisms of the apolipoprotein B (APOB) gene as risk factors for coronary artery disease (CAD), have reported discordant results. The aim of the present study was to search for associations between plasma lipid profiles with the DNA Xba I polymorphism of the APOB gene in CAD patients diagnosed by angiography (CAD+). In the present study we compared 114 Mexican patients (80 men and 34 women) with CAD+ and 132 control patients (59 men and 73 women) without evidence of ischemia or arterial damage (CAD-). The frequency of X+/X+ genotype of Xba I polymorphism, in CAD+ group, was 23% (26/114) compared with 8% (11/132) in the CAD- (OR 3.25, p = 0.002). The patients with X+/X+ for the Xba I genotype APOB gene had higher concentration of triglycerides (TG) and VLDL in plasma than CAD- (p< 0.05). The genotype X+/X+ in the CAD had an effect increasing the TG and VLDL plasma levels when compared with individuals with X-/X- and X-/X+ genotypes. The present study indicated that the X+X+ genotype of Xba I polymorphism is associated with CAD+ patients and high plasma levels of TG and VLDL, in the Mexican population.


Asunto(s)
Apolipoproteínas B/genética , Enfermedad de la Arteria Coronaria/sangre , Enfermedad de la Arteria Coronaria/genética , Lipoproteínas VLDL/sangre , Polimorfismo de Longitud del Fragmento de Restricción , Triglicéridos/sangre , Anciano , Alelos , Enfermedad de la Arteria Coronaria/etnología , Enfermedad de la Arteria Coronaria/fisiopatología , Femenino , Estudios de Asociación Genética , Homocigoto , Humanos , Hipercolesterolemia/etnología , Hipercolesterolemia/genética , Hipertrigliceridemia/etnología , Hipertrigliceridemia/genética , Masculino , México , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Índice de Severidad de la Enfermedad
13.
J Photochem Photobiol B ; 107: 79-83, 2012 Feb 06.
Artículo en Inglés | MEDLINE | ID: mdl-22209030

RESUMEN

Preterm newborns (PNBs) have an immature antioxidant defense system, and this makes them more susceptible to oxidative stress generated by postnatal treatments. The objective was to determine whether micronucleated erythrocytes increase in PNB by postnatal treatments such as oxygentherapy and phototherapy. We counted micronucleated erythrocytes and micronucleated polychromatic erythrocytes as DNA damage in 72 blood samples of PNB at 26-36 weeks of gestation, taken between 1 and 84 h after birth. We assume that more time passed between sampling and birth would correspond to greater time of exposure to oxygen (37 cases) and phototherapy plus oxygen (35 cases). In the PNB only exposed to oxygen, the differences were not significant, while there was a significant increase in micronucleated polychromatic erythrocytes with increasing exposure time in those treated with phototherapy plus oxygen. In conclusion, our results suggest that the MN increase from phototherapy can be observed in peripheral blood erythrocytes of PNB.


Asunto(s)
Núcleo Celular/metabolismo , Eritrocitos/patología , Oxígeno/efectos adversos , Oxígeno/uso terapéutico , Fototerapia/efectos adversos , Nacimiento Prematuro/sangre , Nacimiento Prematuro/terapia , Núcleo Celular/efectos de los fármacos , Núcleo Celular/efectos de la radiación , Daño del ADN , Eritrocitos/efectos de los fármacos , Eritrocitos/metabolismo , Eritrocitos/efectos de la radiación , Femenino , Humanos , Recién Nacido , Leucocitos Mononucleares/efectos de los fármacos , Leucocitos Mononucleares/metabolismo , Leucocitos Mononucleares/patología , Leucocitos Mononucleares/efectos de la radiación , Masculino , Estrés Oxidativo/efectos de los fármacos , Estrés Oxidativo/efectos de la radiación , Nacimiento Prematuro/genética , Nacimiento Prematuro/metabolismo
14.
Mutat Res ; 634(1-2): 126-34, 2007 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-17669682

RESUMEN

Diabetes mellitus (DM) is associated with a high risk of health complications, mainly due to excessive free radical (FRs) production that could result in an increased frequency of micronuclei. The consumption of antioxidants, like folic acid (FA), may mitigate the effects of the FRs. In the present study, micronucleated polychromatic erythrocyte (MNPCE) frequencies were determined in blood sampled weekly from the tails of pregnant female Wistar rats and pregnant Wistar rats with experimental diabetes that were given unsupplemented diets and diets supplemented with FA. At birth, the pups were sampled to analyze micronucleated erythrocyte (MNE) and MNPCE frequencies. Moreover micronucleated cells (MNCs) were evaluated in buccal mucosa samples taken from 81 healthy adult subjects, 48 patients with DM, and 30 DM patients who were sampled before and after FA treatment. Increases in MNPCE frequencies were significant only at the first sampling (P<0.01 and P<0.03) in pregnant rats with experimental diabetes. In addition, the pups from the diabetic group and from diabetic group treated with FA had higher frequencies of MNEs (P<0.03 and P<0.001, respectively) and MNPCEs (P<0.009 and P<0.05, respectively) than the controls. No differences were found in diabetic rats and newborn rats born to diabetic mothers treated with FA compared with untreated animals. Patients with DM had a higher frequency of MNCs compared with healthy subjects (P<0.001). Also FA reduced the frequency of MNCs in DM patients (P<0.001). The results of this study indicate that diabetes results in elevated frequencies of micronuclei, and that, at least in humans, FA can protect against the elevation.


Asunto(s)
Diabetes Mellitus/tratamiento farmacológico , Diabetes Mellitus/genética , Ácido Fólico/uso terapéutico , Adulto , Animales , Animales Recién Nacidos , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/genética , Suplementos Dietéticos , Femenino , Humanos , Masculino , Pruebas de Micronúcleos , Embarazo , Embarazo en Diabéticas/tratamiento farmacológico , Ratas , Ratas Wistar
15.
Environ Mol Mutagen ; 46(4): 253-9, 2005 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-15971258

RESUMEN

Nonhuman primates are of particular relevance in evaluating the potential toxicity of drugs and environmental agents. We have used previously published information and data from the present study to establish a relationship for New World (NW) and Old World (OW) primates on the basis of the frequency of spontaneous micronucleated erythrocytes (MNEs) observed in peripheral blood. Data on spontaneous MNEs in peripheral blood from 15 species of primates, including humans, indicate that NW primates have significantly (P < 0.01) higher MNE frequencies (group mean, 9.5 +/- 7.3 MNEs/10,000 erythrocytes; range, 0.7-20.5/10,000 erythrocytes) than OW primates (group mean, 1.0 +/- 0.9 MNEs/10,000 erythrocytes; range, 0.0-2.6 MNEs/10,000 erythrocytes). Humans are believed to have developed in the OW, and human MNE frequencies were similar to those described for OW primate species. We selected the common marmoset (Callithrix jacchus), a NW primate, to determine whether therapeutic pediatric doses of Metotrexate (MTX; 2.5 mg/kg), Cyclophosphamide (CP; 5 mg/kg), Cytosine-arabinoside (Ara-C; 3 mg/kg), or 5-Fluorouracil (5-FU; 10 mg/kg), administered daily for two consecutive days, increase the frequency of micronuclei. Micronucleated polychromatic erythrocyte frequencies were increased significantly in groups receiving MTX, CP and Ara-C, while MNE frequencies were increased by the Ara-C treatment. The results of this study indicate that NW primates have higher spontaneous MNE frequencies than OW primates, and because of this, NW primates like the common marmoset, may be suitable for evaluating the genotoxicity of chemical agents.


Asunto(s)
Callithrix/sangre , Eritrocitos/efectos de los fármacos , Micronúcleos con Defecto Cromosómico/efectos de los fármacos , Modelos Animales , Mutágenos/toxicidad , Primates/sangre , Animales , Antineoplásicos/toxicidad , Ciclofosfamida/toxicidad , Citarabina/toxicidad , Eritrocitos/patología , Fluorouracilo/toxicidad , Humanos , Metotrexato/toxicidad , Pruebas de Micronúcleos , Pruebas de Mutagenicidad
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