Los excesos del hierro y enfermedades asociadas

[sujal]

Iron, zinc, and alcohol consumption and mortality from cardiovascular diseases:
the Iowa Women's Health Study1,2,3

Duk-Hee Lee, Aaron R Folsom and David R Jacobs, Jr


Background: The relation between iron status and atherosclerosis has long been a topic of debate.

Objective: We examined associations of cardiovascular disease (CVD) mortality with dietary intakes of iron (a possible prooxidant), zinc (a possible antioxidant), and alcohol (a disruptor of iron homeostasis).

Design: Postmenopausal women (n = 34 492) aged 55–69 y at baseline, who completed a food-frequency questionnaire, were followed for CVD mortality over 15 y.

Results: Among women who consumed 10 g alcohol/d, after adjustment for CVD risk factors in a model that contained dietary heme iron, nonheme iron, and zinc intakes, dietary heme iron showed a positive association, dietary nonheme iron showed a U-shaped association, and dietary zinc showed an inverse association with CVD mortality. For example, the relative risks (RRs) for categories of dietary heme iron were 1.0, 1.46, 1.52, 1.73, and 2.47 (P for trend = 0.04); corresponding RRs for dietary nonheme iron were 1.0, 0.93, 0.63, 0.83, and 1.20 (P for quadratic term = 0.02). The corresponding RRs for dietary zinc were 1.0, 0.61, 0.59, 0.57, and 0.37 (P for trend = 0.07). In an analysis restricted to those who consumed 30 g alcohol/d, the risk gradients strengthened.

Conclusions: Our results suggest that a higher intake of heme iron might be harmful, whereas a higher intake of zinc might be beneficial in relation to CVD mortality in the presence of a trigger that can disturb iron homeostasis, such as alcohol consumption.

Conclusiones: Nuestros resultados sugieren que una gran consumo de hierro hemínico podría ser perdjudicial , mientras que alto consumo de zinc podría ser benefico en relación a la muerte por enfermedades cardiovasculares , en presencia de un detonador que altere la homeostasis del hierro, como es el consumo del alcohol.

http://www.ajcn.org/cgi/content/full...type=HWCIT#FN2

[sujal]

Iron: the Redox-active center of oxidative stress in Alzheimer disease.

Castellani RJ, Moreira PI, Liu G, Dobson J, Perry G, Smith MA, Zhu X.
Department of Pathology, University of Maryland, Baltimore, MD, USA.

Although iron is essential in maintaining the function of the central nervous system, it is a potent source of reactive oxygen species. Excessive iron accumulation occurs in many neurodegenerative diseases including Alzheimer disease (AD), Parkinson's disease, and Creutzfeldt-Jakob disease, raising the possibility that oxidative stress is intimately involved in the neurodegenerative process. AD in particular is associated with accumulation of numerous markers of oxidative stress; moreover, oxidative stress has been shown to precede hallmark neuropathological lesions early in the disease process, and such lesions, once present, further accumulate iron, among other markers of oxidative stress. In this review, we discuss the role of iron in the progression of AD.

PMID: 17508283 [PubMed - indexed for MEDLINE]



Traducción
A pesar de que el hierro es esencial en mantener la función del sistema nervioso central, es una fuente potencial de formación de especies reactivas de oxígeno. La acumulación excesiva de hierro ocurre en muchas enfermedades neurodegenerativas incluyendo la Enfermedad de Alzheimer, la enfermedad de Parkinson, y la enfermedad de Creutzfedt Jacob, incrementando la posibilidad de que el estrés oxidativo sea participativo en el proceso de neurodegeneración. El Alzheimer en particular, está asociado con numerosos marcadores de estrés oxidativo. Aun mas, el estrés oxidativo se ha visto que ocurre antes de las lesiones neuropatologicas características, y esas lesiones , una vez presentes , comienzan a acumular hierro, entre otros marcadores de estrés oxidativo.

[natural]

Pero bamos a ver no decian que hay que tomar hierro sino te entra anemia, coño en que quedamos, haber si para alimentarse hay que hacer un master universitario, entre el hierro, el calcio, la b12, las proteina la b6, la b2, la d, y mas elementos importantes ni un nutricionista esta preparado menudo lio.

[sujal]

Heme and non-heme iron consumption and risk of gallstone disease in men
Chung-Jyi Tsai, Michael F Leitzmann, Walter C Willett and Edward L Giovannucci

1 From the Division of Digestive Diseases and Nutrition, University of Kentucky Medical Center, Lexington, Kentucky (C-JT); the Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (C-JT, WCW, and ELG); the Departments of Nutrition and Epidemiology, Harvard School of Public Health, Boston, MA (WCW and ELG); and the Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD (MFL)
2 Supported by research grants (CA55075 and DK46200) from the National Institutes of Health.
3 Reprints not available. Address correspondence to C-J Tsai, Division of Digestive Diseases and Nutrition, University of Kentucky Medical Center, 800 Rose Street, Lexington, Kentucky 40536-0298. E-mail: hpcjt@channing.harvard.edu .



Background:Excessive iron intake can promote biliary cholesterol crystal formation in experimental studies. The absorption of heme iron is more complete than that of non-heme iron in humans; however, the effect of long-term consumption of heme and non-heme iron on the risk of gallstones is unknown
.
Objective:The objective of the study was to examine long-term iron intake in relation to the occurrence of gallstone disease.
Design:We prospectively studied intakes of heme and non-heme iron and the risk of gallstone disease in a cohort of 44 758 US men from 1986 to 2002. Iron consumption was assessed by using a validated semiquantitative food-frequency questionnaire. Newly diagnosed gallstone disease was ascertained biennially.

Results:We documented 2468 incident cases of symptomatic gallstones during 597 699 person-years of follow-up. The age-adjusted relative risks (RRs) for men with intakes of heme iron and non-heme iron, when the highest and lowest quintiles were compared, were 1.21 (95% CI: 1.06, 1.37; P for trend = 0.0008) and 1.02 (95% CI: 0.90, 1.16; P for trend = 0.45), respectively. After adjustment for multiple potential confounding variables, when extreme quintiles were compared, the multivariate RR of heme iron intake was not significantly changed and remained significant with a dose-response relation (RR = 1.21; 95% CI: 1.03, 1.42; P for trend = 0.01), and that of non-heme iron intake was not significant (RR = 1.14; 95% CI: 0.99, 1.31; P for trend = 0.18).

Conclusion:Our findings suggest that a higher consumption of heme iron is associated with a greater risk of gallstone disease among men.

Conclusiones: Nuestros hallazgos sugieren que un elevado consumo de hierro está asociado con un muy elevado riesgo de cálculos biliares entre hombres.

http://www.ajcn.org/cgi/content/abstract/85/2/518

Gallstone disease is very common in Western countries and increasingly is a major cause of abdominal morbidity (1). Approximately 80% of gallstones in Western populations are cholesterol stones (2). Many factors have been associated with the risk of cholesterol gallstones, but cholesterol-saturated bile is an important determinant of gallstone formation (2). High plasma triacylglycerol concentrations are associated with a greater risk of cholesterol gallstones (2).

The human body has a considerable capacity to store iron, but there is no regulated iron excretion in dietary iron overload (3). Homeostatic mechanisms increase iron absorption from the intestine in iron deficiency, but its down-regulation in high intakes of iron, particularly intakes of heme iron, is insufficient to prevent the accumulation of high iron stores (3, 4). Iron is the most abundant transition metal in the body because of its roles in oxygen binding and electron transport (5, 6). During adulthood, iron stores gradually increase almost linearly with age in men (3, 7). Dietary iron overload in adults may be of concern in the United States (8). Elevated iron stores, aside from primary and secondary pathologic forms of iron overload, may be harmful because of their associations with several chronic diseases, including the metabolic syndrome (9-13).

In experimental studies, a high iron diet can elevate plasma triacylglycerol concentrations (14). Iron is a prooxidant prone to produce reactive oxygen metabolites that may promote cholesterol crystal formation in the bile (15). The relation between iron intake and the molar percent cholesterol concentration in the bile in human and animal studies, however, is mixed (16, 17). The effect of long-term iron consumption on the incidence of gallstones in humans is unknown. In a large cohort of US men, we examined long-term iron intake in relation to the occurrence of gallstone disease.

http://ndt.oxfordjournals.org/cgi/content/full/gfl708v1

[sujal]

Pero bamos a ver no decian que hay que tomar hierro sino te entra anemia, coño en que quedamos, haber si para alimentarse hay que hacer un master universitario, entre el hierro, el calcio, la b12, las proteina la b6, la b2, la d, y mas elementos importantes ni un nutricionista esta preparado menudo lio.

Esto va sobre los excesos de hierro.

[natural]

Esto va sobre los excesos de hierro.

Ya por eso que lo mismo no colamos y ala es malo tambien tiene que ser un termino medio, por eso debe uno tener mucho cuidado con los suplementos dichosos que ha veces pueden ser malos, a y tu sigue asi informando, gracias por sacar temas para informar que siempre vienen bien.

[sujal]

[The role of iron in neoplasms]

[Article in Croatian]

Poljak-Blazi M.

Zavod za molekularnu medicinu, Institut Ruder Bosković, Bijenicka cesta 54, 10001 Zagreb.

The purpose of this review is to concisely summarize the current knowledge of iron participation in the carcinogenic process, especially from the standpoint of redox regulation, and to introduce a hypothesis for the mechanism. In both animals and humans, primary neoplasms develop more frequently at body sites of excessive iron deposits. Iron exerts its carcinogenic effects by catalysing formation of hydroxil radicals, suppressing activity of host defence cells and promoting cancer cell multiplication. Manipulations of cellular iron metabolism for modulating normal and malignant cell proliferation is described. Quantitative evaluation of body iron and iron-withholding proteins has prognostic value in cancer patients. Procedures associated with lowering host iron intake and inducing host cell iron efflux can assist in prevention and management of neoplastic disease.

Traducción: En ambos, animals y humanos, neoplasmas primarios se desarrollan mas frecuentemente en lugares del cuerpo donde existen depositos altos de hierro. El hierro ejerce los efectos cancerígenos al catalizar (acelerar) la formación de radicales hidroxilo , supresión de las células defensivas y promoviendo la multiplicación de células cancerígenas. La evaluación cuantitativa de la cantidad de hierro en el organismo, y de proteinas contenedoras de hierro, tiene valor pronóstico para el cáncer. Procedimientos asociados a la baja del consumo de hierro e induciendo a la eliminación del hierro corporal pueden asistir en la prevención y manejo del cáncer.

http://www.ncbi.nlm.nih.gov/pubmed/1...ubmed_RVDocSum

Decreased Cancer Risk After Iron Reduction in Patients With Peripheral Arterial Disease: Results From a Randomized Trial

Leo R. Zacharski, Bruce K. Chow, Paula S. Howes, Galina Shamayeva, John A. Baron, Ronald L. Dalman, David J. Malenka, C. Keith Ozaki, Philip W. Lavori

Background: Excess iron has been implicated in cancer risk through increased iron-catalyzed free radical–mediated oxidative stress.

Methods: A multicenter randomized, controlled, single-blinded clinical trial (VA Cooperative Study #410) tested the hypothesis that reducing iron stores by phlebotomy would influence vascular outcomes in patients with peripheral arterial disease. Patients without a visceral malignancy in the last 5 years (n = 1277) were randomly assigned to control (n = 641) or iron reduction (n = 636). Occurrence of new visceral malignancy and cause-specific mortality data were collected prospectively. Cancer and mortality outcomes in the two arms were compared using intent-to-treat analysis with a Cox proportional hazards regression model. Statistical tests were two-sided.

Results: Patients were followed up for an average of 4.5 years. Ferritin levels were similar in both groups at baseline but were lower in iron reduction patients than control patients across all 6-month visits (mean = 79.7 ng/mL, 95% confidence interval [CI] = 73.8 to 85.5 ng/mL vs 122.5 ng/mL, 95% CI = 115.5 to 129.5 ng/mL; P < .001). Risk of new visceral malignancy was lower in the iron reduction group than in the control group (38 vs 60, hazard ratio [HR] = 0.65, 95% CI = 0.43 to 0.97; P = .036), and, among patients with new cancers, those in the iron reduction group had lower cancer-specific and all-cause mortality (HR = 0.39, 95% CI = 0.21 to 0.72; P = .003; and HR = 0.49, 95% CI = 0.29 to 0.83; P = .009, respectively) than those in the control group. Mean ferritin levels across all 6-monthly visits were similar in patients in the iron reduction and control groups who developed cancer but were lower among all patients who did not develop cancer than among those who did (76.4 ng/mL, 95% CI = 71.4 to 81.4 ng/mL, vs 127.1 ng/mL, 95% CI = 71.2 to 183.0 ng/mL; P = .017).

Conclusions: Iron reduction was associated with lower cancer risk and mortality. Further studies are needed to define the role of body iron in cancer risk.

Conclusiones: la reducción coroporal del hierro, fue asociada con bajos riesgos de desarrollo de cáncer y muerte por cáncer. Mas estudios son necesarios para definir el rol del hiero en el riesgo del cáncer.

Decreased Cancer Risk After Iron Reduction in Patients With Peripheral Arterial Disease: Results From a Randomized Trial

Leo R. Zacharski; Bruce K. Chow; Paula S. Howes; Galina Shamayeva; John A. Baron; Ronald L. Dalman; David J. Malenka; C. Keith Ozaki; Philip W. Lavori
J Natl Cancer Inst. 2008;100(14):996-1002.
©2008 Oxford University Press
Posted 09/15/2008

Abstract and Introduction

Abstract

Background: Excess iron has been implicated in cancer risk through increased iron-catalyzed free radical-mediated oxidative stress.

Methods: A multicenter randomized, controlled, single-blinded clinical trial (VA Cooperative Study #410) tested the hypothesis that reducing iron stores by phlebotomy would influence vascular outcomes in patients with peripheral arterial disease. Patients without a visceral malignancy in the last 5 years (n = 1277) were randomly assigned to control (n = 641) or iron reduction (n = 636). Occurrence of new visceral malignancy and cause-specific mortality data were collected prospectively. Cancer and mortality outcomes in the two arms were compared using intent-to-treat analysis with a Cox proportional hazards regression model. Statistical tests were two-sided.

Results: Patients were followed up for an average of 4.5 years. Ferritin levels were similar in both groups at baseline but were lower in iron reduction patients than control patients across all 6-month visits (mean = 79.7 ng/mL, 95% confidence interval [CI] = 73.8 to 85.5 ng/mL vs 122.5 ng/mL, 95% CI = 115.5 to 129.5 ng/mL; P < .001). Risk of new visceral malignancy was lower in the iron reduction group than in the control group (38 vs 60, hazard ratio [HR] = 0.65, 95% CI = 0.43 to 0.97; P = 036), and, among patients with new cancers, those in the iron reduction group had lower cancer-specific and all-cause mortality (HR = 0.39, 95% CI = 0.21 to 0.72; P = .003; and HR = 0.49, 95% CI = 0.29 to 0.83; P = .009, respectively) than those in the control group. Mean ferritin levels across all 6-monthly visits were similar in patients in the iron reduction and control groups who developed cancer but were lower among all patients who did not develop cancer than among those who did (76.4 ng/mL, 95% CI = 71.4 to 81.4 ng/mL, vs 127.1 ng/mL, 95% CI = 71.2 to 183.0 ng/mL; P = .017).

Conclusions: Iron reduction was associated with lower cancer risk and mortality. Further studies are needed to define the role of body iron in cancer risk.

http://www.ncbi.nlm.nih.gov/pubmed/18612130


Introduction

Body iron stores accumulate imperceptibly with aging because intake exceeds loss and no biologic mechanism exists for excretion of iron in excess of physiological requirements.[1] Iron accumulation has been implicated in the risk of several chronic diseases, including cardiovascular disease and cancer, through increased iron-catalyzed free radical-mediated oxidative stress.[1-9] Clinical cohort studies have found that measures of body iron stores or dietary iron intake may be associated with increased risk of cancer and cancer mortality.[9-14] Colorectal cancer has received particular attention in this regard.[6,11] Cancer risk rises after menopause in women[5,12] in association with rising iron stores.[1] A cause-and-effect relationship between levels of iron stores and cancer risk is suggested by studies showing that blood donation (which reduces body iron) is associated with lower cancer risk[13,14] and that blood transfusion (delivery of an iron load) adversely affects cancer outcome.[15,16] Kato et al. [17] reported a cohort of patients with hepatitis C who were treated with iron reduction and followed for 12 years. These patients had a statistically significantly lower risk of developing hepatocellular carcinoma compared with a demographically similar cohort not treated with iron reduction. Although studies in animal models suggest that limitation or removal of iron may prevent cancer occurrence and growth,[18-20] no such data exist for malignancy in humans.
A randomized trial of calibrated phlebotomy was conducted in patients with advanced peripheral arterial disease.[21-24] Although this clinical trial was designed as a cardiovascular disease study, it provided a setting for controlled, prospective collection of data on risk of new malignancy. The occurrence of new visceral malignancy according to histological type and organ of origin and death according to cause was determined in this cohort of patients, who had no clinical evidence of visceral malignancy within the preceding 5 years.

http://www.medscape.com/viewarticle/578562_1

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[sujal]

Building Your Strength Against Cancer - Iron: The Double-Edged Sword

Iron encourages the formation of cancer-causing free radicals. Of course, the body needs a certain amount of iron for healthy blood cells. But beyond this rather small amount, iron becomes a dangerous substance, acting as a catalyst for the formation of free radicals. Because of this, research studies have shown that higher amounts of iron in the blood mean higher cancer risk (23).

Once iron is absorbed by the digestive tract, the body stores it. Most of us accumulate much more iron than we need. In spite of the advertising from iron supplement manufacturers, "iron overload" is much more common in America than iron deficiency. The reason is the daily diet of red meats, which contributes much more iron than most people can safely handle over the long run. A diet of grains, vegetables, fruits, and beans provides adequate iron, without the risk of overload.

It is easy to check whether your body has accumulated too much stored iron. The following set of tests will check for both iron deficiency and iron overload. The more general hemoglobin and hematocrit tests are not sufficient. Although general guidelines are given here, the tests should be interpreted by your doctor:

Serum ferritin (normal values are 12-200 mcg/l of serum)
Serum iron
Total iron binding capacity (TIBC)

Doctors divide the serum-iron value by the TIBC. The result should be 16 to 50 percent for women and 16 to 62 percent for men. Results above these norms indicate excess iron. Results below these norms indicate iron deficiency. A further test sometimes used to check for iron deficiency is the red cell protoporphyrin test. A result greater than 70 units is considered abnormal. If two of these three values (serum ferritin, serum iron/TIBC, and red cell protoporphyrin) are normal, iron-deficiency anemia is not likely. Serum iron and TIBC should be measured after fasting overnight.

Unfortunately, the body has no way to rid itself of excess iron. Believe it or not, the only way to predictably reduce excessive iron stores is by donating blood. So this altruistic act can have health benefits for the donor as well.

Fuente: The Cancer Porject
http://www.cancerproject.org/protect...ength/iron.php

[Krisnesh]

Pero bamos a ver no decian que hay que tomar hierro sino te entra anemia, coño en que quedamos, haber si para alimentarse hay que hacer un master universitario, entre el hierro, el calcio, la b12, las proteina la b6, la b2, la d, y mas elementos importantes ni un nutricionista esta preparado menudo lio.

Estimado Natural, el tema es mucho mas complejo y simple a la vez, de lo que entendemos.

Se complica por los "pensadores" tradicionales de la nutricion, aquellos que formularon todo lo que hoy comienza a tambalear.

Muchos errores se han cometido en el pasado, por malas investigaciones y por no tener en claro los intererses comerciales activos detras de las investigaciones.....pero como suele decirse, la mentira tiene patas cortas...

El tema es asi: nunca se sacaron los valores recomendados de los nutrientes como promedio de las poblaciones sino que se uso un concepto llamado percentilo - es los porcentajes acumulados hasta llegar al 100 %, es decir el total.

Entonces usando este descriterio , y aceptandose dogmaticamente sin analizar sus pro y sus contras, se confundio a toda la poblacion , incluyendo a los profesionales de salud, con valores de referncias aumentados para cumplir las supuestas deficiencias de grupos poblacinoales con deficiencias mucho mayores que las de los promedios, es decir, para cumplir la necesidades de los percentilos superires.... y acá está el problema con todo.


Yo digo que para el nutriente X el requerimiento nutricional es 100 mg. Entonces, toda la poblacion, sin conocimiento, trata de cumplir en su alimentacion 100 mg de X.
Pero estos 100 mg es el valor que necesistan los que mas neceistan, no la poblacion en general, que tal vez el valor verdadero promedio sea 50 mg.

Entonces todo el mundo está tratando de consmir 50 mg mas de lo que en promedio necesita.

Y los que necesitan solo 25 mg por ej? que pasa?

Y , entonces comienza un tema clave: las sobredosis no son peligrosas? antes no se le daba importancia, tal vez por intereses comerciales y por las muy pocas investigaciones existentes...
Pero hoy, si. Hoy se sabe que el inocente hierro antes asi considerado, es causante de muchisimas enfermdades gravisimas.

Yo pregunté a profesores mios de la materia Nutricion (la catedra de Nutricion de la Facultad de Farmacia y Bioquimica de la UBA , es considerada por muchos como la mas importante en el tema , en la Argentina, y una de las mas importantes de latino america) cuales eran los criterios nutricionales y clinicos para definir por ej anemia ferropenica a partir de cierto valor de hemoglobina en sangre. Ninguno pudo contestar concretamente, solo refirieron su respuesta a que ya estaba estudiado...
Pregunte , por quienes? No lo sabian.

Esta es la realidad: no lo saben, solo han repetido ciegamente conceptos anteriores, sin analizar con profundidad los temas.ESta es la verdad de la ciencia actual.
Por esto soy tan critico , como profesional e investigador, de la misma ciencia a la que pertenezco.

Y estimulo a que todo el mundo estudie, entienda, comprenda los temas con máxima profunidad, por que no es una cuestion de titulo sino de criterio.

Espero que quede claro , Natural , el tema

Saludos

[sujal]

Me gustaría indagar sobre las ventajas e inconvenientes del hierro hemo y no hemo. Quería incidir sobre todo en la duda de si el hierro hemo se regula peor en su absorción y por qué. Para empezar copio las definiciones de las patologías consensuadas en el argot médico por exceso de hierro. Ahora bien, habría que tener en cuenta también todo lo aportado por Krisnesh y concretar otras incidencias sobre un organismo sometido a estrés oxidativo.

Hemosiderosis:

se produce cuando hay una sobrecarga sistémica de hierro, como por ejemplo:

• Aumento en la absorción de hierro en la dieta.
  
• Anemias hemolíticas
  
• Transfusiones sanguíneas (porque los eritrocitos constituyen una fuente de hierro exógeno)
  
• Utilización inadecuada del hierro

El exceso de hierro se deposita en forma de hemosiderina (color amarillo oro, dorado o pardo amarillento) en diferentes tejidos como el hígado, bazo, medula ósea, ganglios linfáticos, piel, páncreas.

En la Hemosiderosis el depósito de hierro en forma de hemosiderina no lesiona la célula, ni altera la función del órgano.


Hemocromatosis:

se caracteriza por la acumulación excesiva de hierro en el organismo (mayor que en la hemosiderosis), que se deposita en forma de hemosiderina en diferentes órganos y tejidos como hígado, bazo, medula ósea, piel páncreas, hipófisis, tiroides, paratiroides, suprarrenal, etc. En este caso la acumulación de hierro en forma de hemosiderina lesiona las células y altera la función del órgano.

La Hemocromatosis puede ser primaria o secundaria.

• Primaria o genética:
  
  se debe a un defecto genético de origen autosómico recesivo que lleva a una absorción excesiva de hierro a nivel intestinal.
  
  
• Secundaria o adquirida:
  
  Aumento en la absorción de hierro en la dieta.
  
  Anemias hemolíticas
  
  Transfusiones sanguíneas (porque los eritrocitos constituyen una fuente de hierro exógeno)

La Hemocromatosis se caracteriza por que el hierro se va depositando a lo largo de la vida y los pacientes presentan cirrosis micronodular, diabetes y pigmentación cutánea. Se caracteriza por que lesiona las células y altera la función del órgano. (lo que la diferencia de la hemosiderosis)


El exceso de hierro produce toxicidad directa en los tejidos del huésped:

1- da lugar a la formación de radicales libres (reacción de Fenton) que produce la peroxidación lipídica de las membranas.

2- Estimula la formación u deposito de colágeno (fibrosis)

3- Alteración en el ADN, por interacción directa del hierro con el ADN.