Estudio morfológico de la neurocarcinogénesis experimental inducida por nitroso-ureas / Morphological study of the experimental neurocarcinogenesis induced by nitrosoureas

En el presente trabajo se hace una revisión de la neurocarcinogénesis química,con especial referencia a los tumores del Sistema Nervioso inducidos por etil-nitrosoureaen la rata Wistar. El estudio morfológico de los tumores del Sistema NerviosoCentral y del Sistema Nervioso Periférico inducidos por exposición prenatala este carcinógeno (50 mg/kg día 17 de gestación) muestra la aparición de tumorescompatibles con un diagnóstico histológico de schwannoma maligno o de oligodendroglioma.Sin embargo, los estudios inmunohistoquímicos y ultraestructuralespermiten clasificar a estos tumores, independientemente de su morfología, comotumores malignos, de tipo neuroectodérmico indiferenciado, con posibilidad dediferenciación hacia líneas neuronales y gliales. Sus características biológicas y suposible diagnóstico in vivo, por medio de Resonancia Magnética, hacen que estemodelo de neurocarcinogénesis sea extraordinariamente útil para valorar el efectode nuevos tratamientos farmacológicos, aplicables a tumores cerebrales malignosen el hombre

This work shows a revision of the chemical neurocarcinogenesis, with specialreference to the Nervous System tumors induced by ethyl-nitrosourea in the Wistarrat. Prenatal administration of this carcinogen (50 mg/kg, day 17 of pregnancy)induces Nervous System tumors with histological features of malignantschwannomas or oligodendrogliomas. However, and independently of theirmorphology, the immunohistochemical and ultrastructural studies allow to classifyto these tumors as undifferentiated malignant tumors, with tumor cells showingpossible differentiation toward neuronal and glial phenotypes. Their biologicproperties and their possible diagnosis in vivo, by means of Magnetic Resonance,make this neurocarcinogenesis model to be extraordinarily useful to value theeffect of new drug treatments, applicable to human malignant brain tumors

Definición de una cohorte para el estudio de la relación entre el mercurio y el cáncer / Definition of a cohort for studying the relationship between mercury and cancer

Objetivos: describir una cohorte de mineros de mercurio y discutir los problemas metodológicos surgidos en la definición de la misma. Se avanzan también resultados preliminares de la mortalidad de los mineros por algunas causas seleccionadas. Población y métodos: la cohorte se construyó en 1.950 a partir de los registros de personal de Minas de Almadén y Arrayanes S.A., y se incluyeron en la misma a los trabajadores que fueron incorporándose en los años siguientes hasta el final del periodo de seguimiento, en 1.994. El seguimiento se completó con la determinación del estado vital y causa básica de defunción, en caso de muerte. Se calcularon las razones de mortalidad estandarizadas según edad, sexo y periodo de calendario. Las muertes esperadas se obtuvieron a partir de las tasas especificas por edad, sexo y periodo de calendario, de la población española. Resultados: el periodo de seguimiento ha sido de 44 años, lo que permite cubrir los periodos de inducción y latencia de las causas de muerte objetivo del estudio, habiendo sido el seguimiento del 92%. Las observaciones realizadas abarcan el periodo comprendido entre 1880 y 1994, siendo el número total de personas-año a riesgo que aportaron los trabajadores expuestos de 103.728. Las primeras causas de muerte en los trabajadores estudiados son las enfermedades cardiovasculares (RME 1,11 IC 95% 1,02-1,20), los cánceres (RME 0,72 IC 95% 0,63-0,82) y las enfermedades respiratorias (RME 1,67 IC 95% 1,46-1,90). .. Conclusiones: la existencia de un exhaustivo fichero de personal bien cuidado en Almadén ha permitido obtener una cohorte dinámica con entradas y salidas a lo largo del tiempo. Sin embargo, en España resulta muy difícil y caro realizar estudios de cohortes debido a las dificultades para completar el seguimiento y conocer el estado vital final de las personas a estudio utilizando los registros nacionales automatizados

Objectives: to describe a cohort of mercury miners and discuss the methodological problems which appeared in its definition. Preliminary results of a mortality analysis by selected causes are also presented. Population and methods: the cohort was assembled in 1950 from the personnel records of Minas de Almadén y Arrayanes S.A. Workers subsequently hiring into the mining company through the end of the follow-up period in 1994 were also included. The follow-up was completed by determination of vital status and, in the case of decedents, by identification of primary cause of death. Standardised mortality ratios by age, sex and calendar period were calculated. Expected deaths were computed based on age-, sex- and calendar period-specific rates for the general Spanish population. Results: the follow-up period was 44 years, which allows for appropriate induction and latency periods of main causes of death; follow-up was 92% complete. The observations cover the period 1880 to 1994, with a total of 103,728 at-risk-person-years among exposed workers. The leading causes of death among workers are cardiovascular diseases(SMR 1,11 CI95% 1,02-1,20), cancer (SMR 0,72 CI 95% 0,63-0,82) and respiratory diseases (SMR 1,67 CI 95% 1,46-1,90). Conclusions: the existence of detailed and meticulously kept personnel records in Almadén has allowed the establishment of a dynamic cohort with entries and exits ayer the study period. However, in Spain it is very difficult and expensive to conduct cohort studies due to difficulties in completing follow-up and ascertainment of vital status based computerised national records

[Training needs and role of general practitioners for preventing measures and medical surveillance of ex-exposed to occupational carcinogens]. / Bisogni formativi e ruolo dei medici di medicina generale per la prevenzione e la sorveglianza sanitaria degli ex esposti a cancerogeni professionali.

The study was aimed at investigating in a sample of general medicine practitioners the level of epidemiologic and law knowledge as well as the degree of sensitivity to the topic of subjects formerly affected by occupational cancer. From the research, carried out on a sample of 745 practitioners from two northern Italy highly industrialized regions, come out the need for training and information on the problems associated with identification and management of subjects formerly exposed to professional cancer.

Dual Association of beta-carotene with risk of tobacco-related cancers in a cohort of French women.

BACKGROUND: Intervention studies have demonstrated that, in smokers, beta-carotene supplements had a deleterious effect on risk of lung cancer and may have a deleterious effect on digestive cancers as well. We investigated a potential interaction between beta-carotene intake and smoking on the risk of tobacco-related cancers in women. METHODS: A total of 59,910 women from the French Etude Epidémiologique de Femmes de la Mutuelle Générale de l'Education Nationale (E3N) prospective investigation were studied from 1994. After a median follow-up of 7.4 years, 700 women had developed cancers known to be associated with smoking. Diet, supplement use, and smoking status at baseline were assessed by self-report. beta-carotene intake was classified into four groups: first (low intake), second, and third tertiles of dietary intake, and use of supplements (high intake). Unadjusted and multivariable Cox proportional hazards models were used to calculate hazard ratios and 95% confidence intervals (CIs) for cancer risk. All statistical tests were two-sided. RESULTS: Among never smokers, multivariable hazard ratios of all smoking-related cancers were 0.72 (95% CI = 0.57 to 0.92), 0.80 (95% CI = 0.64 to 1.01), and 0.44 (95% CI = 0.18 to 1.07) for the second and third tertiles of dietary intake, and high beta-carotene intake, respectively, compared with low intake (Ptrend = .03). Among ever smokers, multivariable hazard ratios were 1.43 (95% CI = 1.05 to 1.96), 1.20 (95% CI = 0.86 to 1.67), and 2.14 (95% CI = 1.16 to 3.97) for the second and third tertiles of dietary intake, and high beta-carotene intake, respectively, compared with low intake (Ptrend = .09). Tests for interaction between beta-carotene intake and smoking were statistically significant (Ptrend =.017). In this population, the absolute rates over 10 years in those with low and high beta-carotene intake were 181.8 and 81.7 cases per 10,000 women in never smokers and 174.0 and 368.3 cases per 10,000 women in ever smokers. CONCLUSIONS: beta-carotene intake was inversely associated with risk of tobacco-related cancers among nonsmokers with a statistically significant dose-dependent relationship, whereas high beta-carotene intake was directly associated with risk among smokers.

Pan masala advertisements are surrogate for tobacco products.

BACKGROUND: Pan masala is a comparatively recent habit in India and is marketed with and without tobacco. Advertisements of tobacco products have been banned in India since 1st May 2004. The advertisements of plain pan masala, which continue in Indian media, have been suspected to be surrogate for tobacco products bearing the same name. The study was carried out to assess whether these advertisements were for the intended product, or for tobacco products with same brand name. MATERIALS AND METHODS: The programme of a popular television Hindi news channel was watched for a 24-h period. Programmes on the same channel and its English counterpart were watched on different days to assess whether the advertisements were repeated. The total duration of telecast of a popular brand of plain pan masala (Pan Parag) was multiplied by the rate charged by the channel to provide the cost of advertisement of this product. The total sale value of the company was multiplied by the proportion of usage of plain pan masala out of gutka plus pan masala habit as observed from a different study, to provide the annual sale value of plain pan masala product under reference. RESULTS: The annual sale value of plain Pan Parag was estimated to be Rs. 67.1 million. The annual cost of the advertisement of the same product on two television channels was estimated at Rs. 244.6 million. CONCLUSION: The advertisements of plain pan masala seen on Indian television are a surrogate for the tobacco products bearing the same name.

The relationship between antioxidant enzymes and bladder cancer.

Carcinogenesis proceeds through at least three distinct stages - initiation, promotion and progression. Free radicals play an important role in the multistep complex course of carcinogenesis. Urinary bladder has been recognized as a target organ for many carcinogens, including benzidine, beta-napthylamine, 2 napthylamine, 4-aminobiphenyl. Antioxidants have been shown to inhibit both initiation and promotion in carcinogenesis. The aim of presented study was to determine and compare the oxidant and antioxidant status in different clinical stages of bladder cancer and of control groups. Study was conducted in fifty-two (n=52) patients with transitional cell epithelial cancer of bladder and in twenty-four (n=24) healthy adults as plasma and erythrocyte controls. Malondialdehyde levels (4.636+/-1.118, 2.853+/-0.576 / 262.112+/-61.772, 203.788+/-35.340) were significantly higher and erythrocyte glutathione levels (6.272+/-1.708, 7.523+/-1.346) were significantly lower in bladder cancer patients group than in control group. Erythrocyte glutathione reductase and glutathione peroxidase (3.935+/-1.155, 5.481+/-1.626 / 8.729+/-1.614, 12.362+/-1.707) activities were significantly lower in cancer patients. In the other hand, glutathione S-transferase activities (3.100+/-1.177, 1.071+/-0.471) were found significantly increases. We suggest that the values of glutathione S-transferase enzyme activity can be used for a tumor detection approach and even as an indicator of the biological behavior of the bladder carcinoma.

Influence of diet on exposure to acrylamide--reflections on the validity of a questionnaire.

AIM: This pilot study attempts to assess how far the standardized questionnaires are a valid tool to detect the food-related burden of acrylamide. Acrylamide is a toxic substance classified by the International Agency of Research on Cancer, as well as the Deutsche Forschungsgemeinschaft, as a probable human carcinogen. METHODS: A venous blood sample was taken in order to determine the smoking-specific acrylnitrile adduct N-cyanoethylvaline and the acrylamide adduct N-2-carbamoylethylvaline in a female study population expecting delivery soon. A standardized questionnaire was used to determine the consumption of acrylamide-contaminated food. The results of our questionnaire were transferred to a linear evaluation system. Finally, anamnestic data of the questionnaire were correlated to objective parameters such as blood levels of hemoglobin adducts of acrylamide and acrylonitrile. RESULTS: A positive correlation between the acrylamide intake and the levels of hemoglobin adducts in our study population was not proven. CONCLUSIONS: Evaluation of food-related exposure to acrylamide is difficult due to several reasons. Firstly, the validity of anamnestic data strongly depends on the patient's ability to remember precisely all consumed food (quality as well as quantity) over a 3-month period. In addition, the contamination of acrylamide in food varies from one product to another; even the contamination of the same product is variable. Therefore, the missing correlation between the questionnaire and hemoglobin adduct rates is rather due to restricted validity of anamnestic data.

Prediction of 2-year carcinogenicity study results for pharmaceutical products: how are we doing?

Some have proposed that 2-year carcinogenicity studies may not be necessary if the material is a direct-acting DNA mutagen, induces liver enzymes, causes hyperplasia or toxicity in particular organs, causes cell proliferation, is cytotoxic, causes hormonal perturbations, or if one has QSAR analyses or 'omics information. Safety pharmacology data, pharmacologic activity, metabolism data, and results of 13-week dose ranging studies (with organ weight data, clinical chemistry data, hematologic data, clinical signs and histopathologic findings) were compared with results of 2-year carcinogenicity studies reviewed by the Center for Drug Evaluation and Research (CDER)/FDA. The experience with the ICH genetic toxicology battery and alternative carcinogenicity models was also reviewed. It appears that the information available from short-term studies is not currently sufficient to accurately and reliably predict the outcome of long-term carcinogenicity studies.

The health effects of diethylstilbestrol revisited.

Although diethylstilbestrol has not been prescribed commonly for more than 25 years, its effects on the health of exposed persons are still important. In this article, we summarize current information about the major health effects of diethylstilbestrol exposure and delineate implications for nurses. Nurses can help to identify persons at risk from prior diethylstilbestrol exposure, facilitate comprehensive assessments of persons exposed to diethylstilbestrol, and share current information about diethylstilbestrol.

Use of treated woods in roof assembly.

On February 12, 2002, the US Environmental Protection Agency (EPA) announced a voluntary decision by industry to move consumer use of treated lumber products away from a variety of pressure-treated wood that contains Arsenate (As) by December 31, 2003, in favor of new alternative wood preservatives. It is the purpose of this report to outline legislative efforts to ban the use of chromated copper arsenate (CCA)-treated wood for residential roofing in the State of Oregon. At the time that the legislation was introduced, it was coincidental that the National Roofing Contractors Association (NRCA) recommended that CCA-treated wood should not be used in residential roofing. A summary of the report is included in this review. Finally, we discuss some of the potentially harmful environmental hazards of wood preservatives on the environment. In addition to the toxicity of pressure-treated wood on our environment, we point out that wood as well as pressure-treated wood assemblies are highly flammable. Consequently, we recommend the use of residential roofing systems that have Class A fire protection for the homeowner. Because residential roof fires remain a life-threatening danger to residential homeowners in the United States, we describe a national fire prevention program for reducing residential roof fires by use of an Underwriters Laboratories Inc. (UL) and National Fire Protection Association Class A fire-rated roof system.

A modified host cell reactivation assay to measure DNA repair capacity for removing 4-aminobiphenyl adducts: a pilot study of bladder cancer.

As DNA repair plays an important role in genetic susceptibility to bladder cancer, assessment of the DNA repair phenotype is critical for the molecular epidemiology of bladder cancer. In this study, we developed and applied an assay using the luciferase (luc) reporter gene in a host-cell reactivation assay to measure DNA repair capacity for DNA damage induced by 4-aminobiphenyl (4-ABP), a well-studied aromatic amine and a known bladder carcinogen. We observed a dose-response relationship for 4-ABP dosage and DNA repair capacity (luc activity). We then applied this assay to measure DNA repair capacity in a pilot study of 89 pairs of bladder cancer patients and healthy controls matched by age, gender, and ethnicity, and we found that DNA repair capacity was significantly lower in cases than in controls (13.0% versus 14.4%; P = 0.006). Poor DNA repair capacity was associated with 3.42-fold increased bladder cancer risk. Further analysis revealed that intermediate and low levels of DNA repair capacity increased bladder cancer risk to 3.43-fold and 4.97-fold, respectively, compared with individuals with the most efficient DNA repair capacity. Moreover, ever smokers with suboptimal DNA repair capacity exhibited a 6.06-fold increased risk compared with never smokers with normal DNA repair capacity. In conclusion, our results support the hypothesis that deficient DNA repair capacity for 4-ABP induced DNA damage and increases bladder cancer risk. Our assay provides a new tool to specifically quantify DNA repair capacity in bladder cancer studies and, therefore, contributes to our goal of further elucidating bladder carcinogenesis.

[Health risk related to municipal waste incineration]. / Ryzyko zdrowotne zwiazane ze spalaniem odpadów komunalnych.

There are exposures to various organic and inorganic xenobiotics related to municipal waste incineration in work places and environment close to incinerators. Among others, these are polychlorinated biphenyls, dioxins, furans, chlorophenols, mono- and polycyclic aromatic hydrocarbons, toxic metals and irritation gases. Numerous studies revealed that these chemicals and their metabolites were generally not elevated in worker's blood and urine and in persons living near incinerators. The epidemiological studies indicate increased cancer risk and excess of ischemic heart disease in incinerator workers. In residents living in the vicinity of incinerators, a slightly increased cancer risk, respiratory symptoms, multiple pregnancy, congenital abnormalities, and disturbances in thyroid hormone levels were observed. However, these data do not provide univocal evidence that the cause-effect relationship between exposure and health risk does really exist.

Long-term dysregulation of circadian and 17-beta estradiol-induced LH, prolactin and corticosterone secretion after dimethylbenz (a) anthracene administration in the Sprague-Dawley female rat.

A single intragastric administration of 7,12-dimethylbenz (a) anthracene (DMBA) has been shown, when given at 55-60 days of age, to induce mammary tumors in young cycling female Sprague-Dawley rats. The appearance of the tumors is preceded by a series of neuroendocrine disturbances of the hypothalamo-pituitary-gonadal (HPG) axis, including attenuation of the preovulatory Luteinizing Hormone (LH) and Gonadotropin-Releasing Hormone (GnRH) release and amplification of the preovulatory 17beta-Estradiol (E(2)) surge. In this study, we examined the hypothesis that a single administration of DMBA could also, in the long range, induce disturbances of others neuroendocrine axis, like the Hypothalamic-Pituitary-Adrenal (HPA) axis and/or the Lactotroph axis. Sprague-Dawley rats, 55-60 days of age, received, on the day of Estrous of the Estrous cycle, a single administration of 15 mg of DMBA delivered by intragastric intubation. Then, they were ovariectomized 5 days later. One month later, (1) Two groups of animal were sacrificed by decapitation at 09:00 a.m. and 05:00 p.m. to record the circadian rhythm of plasma LH, Prolactin (PRL) and corticosterone, (2) Three other groups of animal were sacrificed by decapitation at three different times after a morning subcutaneous administration of 50 microg/kg of Estradiol Benzoate (EB), to induce a negative and positive feed-back of the secretion of LH. Then, plasma LH, PRL and corticosterone concentrations were measured. After DMBA administration, (1) the negative--but not the positive--LH feed-back was seen, (2) the PRL circadian rhythm was blunted and the corticosterone circadian rhythm was almost absent, (3) the increase in PRL or Corticosterone plasma concentration was significantly reduced. In conclusion, a single administration of DMBA provokes a long-term dysregulation of not only the HPG axis but also of the lactotroph and HPA axis. These dysregulations, along with the already evidenced long-term inhibition of DMBA upon Melatonin secretion from the pineal gland, might accelerate the promotion of mammary tumors induced by the mammary carcinogen.

[Microbiological degradation of benz(a)pyrene in soil].

Several microbial clones that could grow on the benz(a)pyrene medium were identified from the soils contaminated with petroleum products. It was shown that benz(a)pyrene could be degraded by the obtained cultures that selectively utilized the carcinogenic molecules of benz(a)pyrene in the presence of other sources of carbohydrate. The authors give recommendations on the biodestruction of benz(a)pyrene and other polycyclic aromatic hydrocarbons under natural conditions in order to improve the oncoecological situation.