Dietary hemin promotes colonic preneoplastic lesions and DNA damage but not tumor development in a medium-term model of colon carcinogenesis in rats.

Red and processed meat consumption has been strongly related to increase the risk of colorectal cancer (CRC), although its impact is largely unknown. Hemin, an iron-containing porphyrin, is acknowledged as a putative factor of red and processed meat pro-carcinogenic effects. The aim of this study was to investigate the effects of high dietary hemin on the promotion/progression stages of 1,2-dimethylhydrazine (1,2-DMH)-induced colon carcinogenesis. Twenty-four Wistar male rats were given four subcutaneous 1,2-DMH injections and received either balanced diet or balanced diet supplemented with hemin 0.5 mmol/kg for 23 weeks. Colon specimens were analyzed for aberrant crypt foci (ACF) and tumor development. Dietary hemin significantly increased ACF number and fecal water cytotoxicity/genotoxicity in Caco-2 cells when compared to 1,2-DMH control group. However, tumor incidence, multiplicity and cell proliferation did not differ between 1,2-DMH + hemin and 1,2-DMH control group. Gene expression analysis of 91 target-genes revealed that only three genes (Figf, Pik3r5 and Tgfbr2) were down-regulated in the tumors from hemin-fed rats compared to those from 1,2-DMH control group. Therefore, the findings of this study show that high hemin intake promotes mainly DNA damage and ACF development and but does not change the number nor incidence of colon tumors induced by 1,2-DMH in male rats.

Subcutaneous injection of multipotent mesenchymal stromal cells admixed with melanoma cells in mice favors tumor incidence and growth: a systematic review and meta-analysis.

Multipotent mesenchymal stem/stromal cells (MSCs) have strong tropism towards cancer cells, thus being tested as tools for the targeted delivery of therapeutic substances for the treatment of melanoma. However, different experimental approaches for melanoma induction and MSC treatment can have a direct impact on the outcomes. Systematic search was carried out in three databases (PubMed, Scopus, and Web of Science) to include all studies, where stem cells were used as intervention for animal models for melanoma. Selected articles were classified according to SYRCLE's risk of bias tool for animals' studies. Experimental variables and published data for tumor incidence and growth were extracted from the eligible articles and standardized using Hedge's G for random effects meta-analysis and meta-regression. From 627 entries, 11 articles were eligible for meta-analysis. All studies tested the effects of a single injection of mesenchymal stem/stromal cells (MSCs) (from bone marrow or adipose tissue) admixed with B16 mouse melanoma cells (B16-F0 or B16-F10) or with human melanoma cells (A375 or M4Beu) in mice. Mean SYRCLE score was 3.09 out of 10. Results from random effects meta-analysis indicate that MSCs favored both tumor incidence and tumor growth (p = 0.001) in melanoma. Our results show that MSCs are protumorigenic in co-injection mice models for melanoma, increasing both tumor incidence and growth.

Enhancement of colon carcinogenesis by the combination of indole-3 carbinol and synbiotics in hemin-fed rats.

The risk of developing colorectal cancer (CRC) could be associated with red and processed meat intake. Experimental data supports that hemin iron, found abundantly in red meat, promotes CRC in mice and rats, while indole-3 carbinol (I3C) and synbiotics (syn) exert anti-carcinogenic activities in most studies of colon carcinogenesis. This study aimed to investigate the modifying effects of I3C and syn (inulin + Bifidobacterium lactis), given separately or together, on dimethylhidrazine (DMH)-induced colon carcinogenesis in hemin-fed rats. All animals were given four subcutaneous DMH injections and then, two weeks after carcinogen exposure, they began a basal diet containing hemin, hemin + I3C, hemin + syn, or hemin + I3C + syn for 23 weeks. The combination of I3C + syn significantly increased fecal water genotoxicity, tumor volume and invasiveness when compared to the hemin-fed control group. The groups fed I3C or syn alone had a significant reduction in the number of preneoplastic aberrant crypt foci (ACF) lesions compared to the hemin-fed group. Dietary I3C also reduced fecal water genotoxicity. Gene expression analysis of colorectal tumors demonstrated that the combination of dietary I3C + syn increased transcript levels for Raf1 and decreased tumor progression and invasiveness related to the genes Cdh1 and Appl1. This analysis also revealed that the Tnf and Cdh1 genes were significantly up- and down-regulated, respectively, in tumors of rats that received I3C, in comparison with the hemin-fed group. These findings reveal that the joint administration of I3C and syn enhanced the development of colon tumors induced by DMH in hemin-fed rats, while they potentially reduced ACF development when given alone.

Arsenic and ultraviolet radiation exposure: melanoma in a New Mexico non-Hispanic white population.

Cases of cutaneous melanoma and controls were enrolled in a New Mexico population-based study; subjects were administered questionnaires concerning ultraviolet (UV) and inorganic arsenic (iAs) exposure. Historical iAs exposure was estimated. UV exposure estimates were also derived using geospatial methods. Drinking water samples were collected for iAs analysis. Blood samples were collected for DNA repair (Comet) and DNA repair gene polymorphism assays. Arsenic concentrations were determined in urine and toenail samples. UV exposures during the previous 90 days did not vary significantly between cases and controls. Mean (±SD) current home iAs drinking water was not significantly different for cases and controls [3.98 µg/L (±3.67) vs. 3.47 µg/L (±2.40)]. iAs exposure showed no effect on DNA repair or association with melanoma. Results did not corroborate a previously reported association between toenail As and melanoma risk. Arsenic biomarkers in urine and toenail were highly significantly correlated with iAs in drinking water. A UV-DNA repair interaction for UV exposure over the previous 7-90 days was shown; cases had higher DNA damage than controls at low UV values. This novel finding suggests that melanoma cases may be more sensitive to low-level UV exposure than are controls. A UV-APEX1 interaction was shown. Subjects with the homozygous rare APEX1 DNA repair gene allele had a higher risk of early melanoma diagnosis at low UV exposure compared with those with the homozygous wild type or the heterozygote. Notably, a UV-arsenic interaction on inhibition of DNA repair was not observed at iAs drinking water concentrations below 10 ppb (µg/L).

Cutaneous changes in rats induced by chronic skin exposure to ultraviolet radiation and organophosphate pesticide.

PURPOSE: To study the possible potentiation of the carcinogenic effects of ultraviolet radiation associated with an organophosphate pesticide. METHODS: Forty Wistar rats were assigned into four groups (n=10 each) randomized according to the procedures: group A received only UVR-B radiation; group B, UVR-B for eight weeks followed by a seven week period of pesticide exposure; group C, UVR-B + pesticide concomitantly: group D, only pesticide application. At the end of the fifth, tenth and fifteenth weeks the animals were photographed. Skin biopsy and histopathological study with Hematoxylin-Eosin were done on the fifteenth week. Statistical analysis with Fisher's and Sign (unilateral) tests, 5% value for significance. RESULTS: Macroscopic lesions in the group A evolved from the erythema to erythema + desquamation. The groups B and C, with the association of two carcinogens, and group D presented evolution to keratosis, with higher incidence in group D. The histology showed a significant increase in the severity of injuries when the UVR-B and the pesticide were applied simultaneously, leading to cellular atypia. CONCLUSIONS: Concurrent association of UVR-B to organophosphate pesticide produced more severe lesions microscopically, although this has not been so apparent macroscopically. In daily practice the clinical evaluation should be complemented with laboratory evaluation.

Mouthwashes with hydrogen peroxide are carcinogenic, but are freely indicated on the Internet: warn your patients!

It all began in Ancient Egypt where people used to bleach their teeth with antiseptic mouthwashes made of urea from human urine. Teeth harmony is promoted by expression of feelings, communication, a real window of the brain and its content! Tooth bleaching products are medicines, not cosmetics! Mouth washing with hydrogen peroxide is an illogical and dangerous procedure! Hydrogen peroxide must be used in one's mouth only when employed by a dentist who has been properly instructed to protect the mucosa, preventing it from receiving these products. How and for how long these products are going to be used require caution in order to avoid or decrease any adverse effects on the tissues. Many websites instruct people on how to purchase and prepare hydrogen peroxide so that it is used as an antiseptic mouthwash and tooth bleaching agent. Some websites even refer to dentists as "exploiters", accusing them of not instructing patients properly. In this article, we aim at providing evidence and information upon which dentists and assistants may base their thinking as well as their opinion and procedures regarding "the indiscriminate and free use of hydrogen peroxide in the mouth, on teeth and oral mucosa". Those websites, blogs and social network profiles trespass the limits of public trust and should be immediately sued by the government for committing a crime against public health.

Mouthwashes with hydrogen peroxide are carcinogenic, but are freely indicated on the internet: warn your patients!

It all began in Ancient Egypt where people used to bleach their teeth with antiseptic mouthwashes made of urea from human urine. Teeth harmony is promoted by expression of feelings, communication, a real window of the brain and its content! Tooth bleaching products are medicines, not cosmetics! Mouth washing with hydrogen peroxide is an illogical and dangerous procedure! Hydrogen peroxide must be used in one's mouth only when employed by a dentist who has been properly instructed to protect the mucosa, preventing it from receiving these products. How and for how long these products are going to be used require caution in order to avoid or decrease any adverse effects on the tissues. Many websites instruct people on how to purchase and prepare hydrogen peroxide so that it is used as an antiseptic mouthwash and tooth bleaching agent. Some websites even refer to dentists as "exploiters", accusing them of not instructing patients properly. In this article, we aim at providing evidence and information upon which dentists and assistants may base their thinking as well as their opinion and procedures regarding "the indiscriminate and free use of hydrogen peroxide in the mouth, on teeth and oral mucosa". Those websites, blogs and social network profiles trespass the limits of public trust and should be immediately sued by the government for committing a crime against public health.

Tudo começou no Egito antigo, onde procurava-se clarear os dentes com bochechos antissépticos com ureia da urina humana. Os dentes se harmonizam com expressões de sentimentos, na comunicação, como uma verdadeira vitrine do cérebro e seus conteúdos! Clareadores dentários são medicamentos, e não cosméticos! Bochecho com água oxigenada representa um procedimento improcedente e perigoso! O uso do peróxido de hidrogênio ou água oxigenada na boca deve ser feito diretamente pelo profissional da Odontologia, treinado para proteger as mucosas contra o contato desses produtos. O tempo e a forma de uso requerem cuidados, para se proteger ou diminuir os efeitos indesejáveis sobre os tecidos. Vários websites "ensinam" como adquirir e preparar água oxigenada para fazer bochechos antissépticos e clarear os dentes. Alguns websites se referem ao profissional da Odontologia como um "explorador", por não ensinar isso ao paciente. No presente artigo, procuraremos informar e dar fundamentos para que os profissionais da Odontologia e auxiliares possam embasar suas reflexões, opiniões e condutas relacionadas ao tema "uso indiscriminado e livre de peróxido de hidrogênio na boca sobre os dentes e mucosa bucal". Esses websites, blogs e perfis em redes sociais abusam da fé pública e deveriam ser acionados judicialmente, imediatamente, pelas autoridades públicas, pelo crime contra a saúde das pessoas.

Fitas adesivas, "Vanish" e técnica clareadora caseira: aspectos importantes a serem considerados / Adesive tapes

Em trabalhos experimentais, o peróxido de hidrogênio revelou-se um promotor da carcinogênese química bucal e em outras mucisas gastrintestinais. O peróxido de hidrogênio representa um cocarcinógeno, pois não inicia sozinho uma neoplasia maligna epitelial, mas pode potencializar outros agentes iniciadores. Na boca, onde atuam vários carcinógenos, a mucosa está, em sua maior aprte, desprotegida, pois não tem em sua superfície uma espessa e contínua camada de queratina, como a pele. Em qualquer forma de ação, o peróxido de hidrogênio - o único clareador de dentes - requer técnica que proteja a mucosa e a região cervical do esmalte na junção com o cemento, e dificulte que seja engolido, indo para as partes mais inferiores do trato gastrintestinal. Este trabalho centra-se principalmente na necessidade de convencer pacientes, profissionais e agentes do mercado de que a forma mais correta e segura de clarear dentes está no consultório dos profissionais treinados e conscientes

Cytogenetic biomonitoring in oral mucosa cells following dental X-ray.

OBJECTIVES: In the past decades, X-rays have been used widely for diagnosis in dentistry. However, it is well known that ionizing radiation causes damage (including single- and double-strand breaks) to deoxyribonucleic acid (DNA) and DNA-protein crosslinks, and induces cellular death. Therefore, outlining the cytogenetic effects induced by X-ray is necessary to identify the degree of cancer risk and minimize potential risks to patients and clinicians. To date, a variety of assays have been proposed in cytogenetic biomonitoring studies, including those that assess metaphase chromosomal aberrations and sister chromatid exchanges, and micronucleus and single-cell gel (comet) assay. METHODS: Cytogenetic biomonitoring studies focusing on oral mucosa cells in individuals exposed to dental X-ray were reviewed. RESULTS: Dental X-ray can induce DNA damage and cytotoxicity in oral mucosa cells. CONCLUSION: These results will contribute to a better understanding of X-ray-induced effects upon the cellular system in individuals continually exposed to known genotoxic/cytotoxic agents.

Alterations in c-Src/HER1 and estrogen receptor α signaling pathways in mammary gland and tumors of hexachlorobenzene-treated rats.

Hexachlorobenzene (HCB) is an organochlorine pesticide that acts as an endocrine disruptor in humans and rodents. The development of breast cancer strongly depends on endocrine conditions modulated by environmental factors. We have demonstrated that HCB is a tumor co-carcinogen in rats and an inducer of proliferation in MCF-7 cells, in an estrogen receptor α (ERα)-dependent manner, and of migration in MDA-MB-231 breast cancer cell line. In the present study, we examined HCB effect on c-Src/human epidermal growth factor receptor (HER1) and ERα signaling pathways in mammary glands and in N-nitroso-N-methylurea (NMU)-induced mammary tumors in rats. Furthermore, we evaluated histopathological changes and serum hormone levels. Rats were separated into four groups: control, HCB (100 mg/kg b.w.), NMU (50 mg/kg b.w.) and NMU-HCB. Our data show that HCB increases c-Src and HER1 activation, c-Src/HER1 association, and Y699-STAT5b and ERK1/2 phosphorylation in mammary glands. HCB also enhances Y537-ERα phosphorylation and ERα/c-Src physical interaction. In tumors, HCB also induces c-Src and HER1 activation, c-Src/HER1 association, as well as T308-Akt and Y699-STAT5b phosphorylation. In addition, the pesticide increases ERα protein content and decreases p-Y537-ERα levels and ERα/c-Src association in tumors. HCB increases serum 17-beta estradiol and prolactin contents and decreases progesterone, FSH and LH levels in rats without tumors, while the opposite effect was observed in rats with tumors. Taken together, our results indicate that HCB induces an estrogenic effect in mammary gland, increasing c-Src/HER1 and ERα signaling pathways. HCB stimulates c-Src/HER1 pathway, but decreases ERα activity in tumors, appearing to shift them towards a higher malignancy phenotype.

Carcinogénesis

La división celular es controlada por una serie de sistemas que tienen efectos estimulantes o inhibitorios.El cáncer es de origen monoclonal, y para que una célula normal cambie su fenotipo y se convierta en una célula neoplásica deben ocurrir mutaciones genéticas en la misma.Dichas mutaciones genéticas ocasionan la modificación de los productos que en condiciones normales codificaría el gen y,finalmente,a un cáncer.El cáncer resultante puede ser hereditario (por mutaciones en uno o ambos alelos de las células germinales) o esporádico (por la acción de agentes mutágenos ambientales).A su vez, los mecanismos que pueden conducir a alteraciones en los genes pueden ser genéticos o epigenéticos; los primeros se presentan ante alteraciones estructurales del genoma y los restantes, epigenéticos, por alteraciones de las enzimas o de los sustratos de las mismas.La carcinogénesis consta de tres etapas:iniciación,promoción y progresión.La última de estas etapas,progresión,es exclusiva de la transformación maligna e implica la capacidad de invadir tejidos vecinos o a distancia. Para que se lleve a cabo el proceso metastásico, se requiere de una serie de mecanismos: angiogénesis, degradación de matrices, migración celular, evasión de la respuesta inmune del hospedero y colonización metastásica. Este artículo representa una revisión parcial de la bibliografía actualizada de los conceptos relacionados a la carcinogénesis y la información mínima necesaria para lograr un entendimiento de este complejo proceso.

Cell division is controlled by stimulatory and inhibitory systems.The origin of cancer is monoclonal, and in order that a normal cell switches its phenotype and becomes a neoplastic cell, genetic mutations must occur on it.These genetic mutations modify the products that in normal conditions the gene would codify and, finally, cause cancer. Cancer may be hereditary (due to mutations in one or both of germinal cells alleles) or sporadic (due to action of environmental mutagenic agents).The mechanisms that may cause alterations on genes may be genetic or epigenetic. Genetic mechanisms occur when structural alterations of genome are present and the epigenetic processes occur due to enzymatic alterations or alterations on its substrates. Carcinogenesis has three stages: initiation, promotion and progression.The last of these stages, progression, is exclusive of malignant transformation and implies the capacity to invade surrounding or distant tissues. For metastasis to take place, many mechanisms are required: angiogenesis, matrix degradation, cell migration, evasion of host immune response and metastatic colonization. This article presents a partial review of current bibliography about concepts related to carcinogenesis and conveys the minimum necessary information to achieve an understanding of this complex process.

Diet and breast cancer

Both diet and nutrition have been studied in relationship with breast cancer risk, as the great variation among different countries in breast cancer incidence could possibly be explained through the inflammatory and immune response, as well as antioxidant intake, among others.To date, no clear association with diet beyond overweight and weight gain has been found, except for alcohol consumption. Nonetheless, the small number of studies done in middle to low income countries where variability of food intake is wider,is beginning to show interesting results.

Tanto la dieta como la nutrición han sido estudiadas en relación con el riesgo de cáncer de mama, dada la gran variación de incidencia de cáncer entre países, y la posibilidad de explicarla a través de la respuesta inflamatoria o inmune, así como ingesta de antioxidantes,entre otros.Hasta la fecha, ninguna asociación clara con la dieta ha sido encontrada, excepto para el consumo de alcohol, más allá del sobrepeso y del incremento de peso. Sin embargo, los estudios que se están realizando en países de mediano a bajo nivel de ingresos, con mayor variabilidad de ingesta de alimentos, comienzan a mostrar resultados interesantes.

Alcohol consumption and the risk of breast cancer

Epidemiologic studies addressing the association of alcohol consumption with breast cancer consistently suggest a modest association and a dose-response relationship. The epidemiologic evidence does not point to a single mechanism to explain the association, and several mechanisms have been proposed. Alcohol consumption is shown to increase levels of endogenous estrogens, known risk factors for breast cancer. This hypothesis is further supported by data showing that the alcohol-breast cancer association is limited to women with estrogen-receptor positive tumors. Products of alcohol metabolism are known to be toxic and are hypothesized to cause DNA modifications that lead to cancer. Recent research has focused on genes that influence the rate of alcohol metabolism, with genes that raise blood concentrations of acetaldehyde hypothesized to heighten breast cancer risk. Mounting evidence suggests that antioxidant intake(e.g.folate)mayreducealcohol-associatedbreast cancer risk, because it neutralizes reactive oxygen species, a second-stage product of alcohol metabolism. Diets lacking sufficient antioxidant intake, as a result, may further elevate the risk of breast cancer among alcohol consumers. Given that alcohol consumption is increasing worldwide and especially among women in countries of rapid economic growth, a greater understanding of the mechanisms underlying the known alcohol-breast cancer association is warranted.Avoiding overconsumption of alcohol is recommended, especially for women with known risk factors for breast cancer.

Diversos estudios epidemiológicos muestran la asociación del consumo de alcohol con el cáncer de mama de forma consistente, lo que sugiere una modesta asociación, y una relación de dosis-respuesta.La evidencia no apunta a un mecanismo único para explicar la asociación y varios mecanismos han sido propuestos. El consumo de alcohol incrementa los niveles endógenos de estrógeno, un riesgo conocido para cáncer de mama. Esta hipótesis es apoyada por información que muestra que la asociación entre el alcohol y el cáncer de mama está limitada a mujeres con tumores con receptores positivos de estrógeno. Es conocido que los derivados de la metabolización del alcohol son tóxicos, y se ha pensado que causan modificaciones en el DNA que llevan al cáncer. La investigación reciente se ha enfocado en genes que influencian la velocidad con la que se metaboliza el alcohol, y elevan las concentraciones de acetaldehído que se piensa puede aumentar el riesgo de cáncer de mama. La evidencia actual sugiere que la ingesta de antioxidantes (e.g. folato) puede reducirelriesgode cáncer asociadoalalcohol,porque neutraliza las especies reactivas de oxígeno, un producto de la segunda etapa del metabolismo del alcohol. Las dietas con ingesta insuficiente de antioxidantes,como resultado de esto, pueden elevar el riesgo de cáncer entre los consumidores de alcohol.Dado que el consumo de alcohol está incrementando en todo el mundo, especialmente en mujeres de países con rápido crecimiento económico, un mejor entendimiento de los mecanismos subyacentes a la asociación del cáncer de mama y el alcohol es necesario. Evitar el consumo excesivo es recomendado, especialmente para mujeres con factores de riesgo conocidos para cáncer de mama.

N-Nitrosodiethylamine genotoxicity in primary rat hepatocytes: effects of cytochrome P450 induction by phenobarbital.

Primary hepatocytes are widely used in investigating drug metabolism and its toxicological effects. N-Nitrosodiethylamine (NDEA)-induced genotoxicity and cytotoxicity was used in primary cultures of female rat hepatocytes in the presence of phenobarbital (PB). PB pre-treatment (1mM) increased the number of necrotic (2-fold) and apoptotic cells (4-fold) after NDEA treatment (0.21-105 µg/mL). The mitotic indices and the number of micronucleated cells decreased, thus suggesting cytotoxicity. An increased number of chromosomal aberrations were observed after pre-treatment with PB. NDEA-treatment (0.21-21 µg/mL) induced expression of the CYP2B1 and CYP2B2 mRNA and PB treatment alone induced ~6-fold and ~2-fold increases of CYP2B1 and CYP2B2 mRNA, respectively. NDEA treatment following PB exposure increased CYP2B1 mRNA expression under all tested concentrations and also increased CYP2B2 expression at 21 and 105 µg/mL. Our data suggest that the alteration of CYP2B1/2 expression by PB increased the cytotoxicity and genotoxicity of NDEA leading to the final genotoxic metabolite.

[Carcinogenesis]. / Carcinogénesis.

Cell division is controlled by stimulatory and inhibitory systems.The origin of cancer is monoclonal, and in order that a normal cell switches its phenotype and becomes a neoplastic cell, genetic mutations must occur on it.These genetic mutations modify the products that in normal conditions the gene would codify and, finally, cause cancer. Cancer may be hereditary (due to mutations in one or both of germinal cells alleles) or sporadic (due to action of environmental mutagenic agents).The mechanisms that may cause alterations on genes may be genetic or epigenetic. Genetic mechanisms occur when structural alterations of genome are present and the epigenetic processes occur due to enzymatic alterations or alterations on its substrates. Carcinogenesis has three stages: initiation, promotion and progression.The last of these stages, progression, is exclusive of malignant transformation and implies the capacity to invade surrounding or distant tissues. For metastasis to take place, many mechanisms are required: angiogenesis, matrix degradation, cell migration, evasion of host immune response and metastatic colonization. This article presents a partial review of current bibliography about concepts related to carcinogenesis and conveys the minimum necessary information to achieve an understanding of this complex process.

Alcohol consumption and the risk of breast cancer.

Epidemiologic studies addressing the association of alcohol consumption with breast cancer consistently suggest a modest association and a dose-response relationship. The epidemiologic evidence does not point to a single mechanism to explain the association, and several mechanisms have been proposed. Alcohol consumption is shown to increase levels of endogenous estrogens, known risk factors for breast cancer. This hypothesis is further supported by data showing that the alcohol-breast cancer association is limited to women with estrogen-receptor positive tumors. Products of alcohol metabolism are known to be toxic and are hypothesized to cause DNA modifications that lead to cancer. Recent research has focused on genes that influence the rate of alcohol metabolism, with genes that raise blood concentrations of acetaldehyde hypothesized to heighten breast cancer risk. Mounting evidence suggests that antioxidant intake(e.g.folate)mayreducealcohol-associatedbreast cancer risk, because it neutralizes reactive oxygen species, a second-stage product of alcohol metabolism. Diets lacking sufficient antioxidant intake, as a result, may further elevate the risk of breast cancer among alcohol consumers. Given that alcohol consumption is increasing worldwide and especially among women in countries of rapid economic growth, a greater understanding of the mechanisms underlying the known alcohol-breast cancer association is warranted. Avoiding overconsumption of alcohol is recommended, especially for women with known risk factors for breast cancer.

Diet and breast cancer.

Both diet and nutrition have been studied in relationship with breast cancer risk, as the great variation among different countries in breast cancer incidence could possibly be explained through the inflammatory and immune response, as well as antioxidant intake, among others. To date, no clear association with diet beyond overweight and weight gain has been found, except for alcohol consumption. Nonetheless, the small number of studies done in middle to low income countries where variability of food intake is wider, is beginning to show interesting results.

Absence of chemopreventive influence of propolis on the rat liver altered foci development.

Propolis (bee glue) is a complex mixture of natural substances that exhibits a broad spectrum of biological activities. As the possibility exists that it may exert a chemopreventive role against cancer development, the present study aimed to evaluate the chemopreventive influence of a Brazilian aqueous propolis extract (APE) in a rat two-stage (initiation-promotion) medium-term bioassay for chemical liver carcinogenesis. Male Wistar rats were sequentially initiated with diethylnitrosamine (DEN, 200mg/kgb.w.) and, 2 weeks later, exposed to a diet containing hexachlorobenzene (HCB, 100ppm) and to APE 0.1% through drinking water for 6 weeks. Appropriate control groups were also established. The animals were sacrificed at the weeks 8th and 30th when liver samples were processed to evaluate the development of altered hepatocyte foci (AHF) identified under hematoxylin and eosin (H&E) staining and by the immunohistochemical expression of the enzyme glutathione S-transferase placental form (GST-P). The results indicate that APE 0.1% did not protect against the development of any of the differentially identified putative preneoplastic foci in DEN-initiated animals, exposed or not to the promoting agent HCB. Also, APE 0.1% by itself did not significantly induce any AHF, what is in line with its already known absence of genotoxic potential. Our results indicate that an aqueous extract of Brazilian propolis did not exert chemoprevention on the hepatocarcinogenesis process chemically induced in the rat.

Diet and serum micronutrients in relation to cervical neoplasia and cancer among low-income Brazilian women.

Cervical cancer is a leading cancer among women in developing countries. Infection with oncogenic human papillomavirus (HPV) types has been recognized as a necessary cause of this disease. Serum carotenoids and tocopherols have also been associated with risk for cervical neoplasia, but results from previous studies were not consistent. We evaluated the association of serum total carotene and tocopherols, and dietary intakes with the risk of newly diagnosed, histologically confirmed cervical intraepithelial neoplasia (CIN) grades 1, 2, 3 and invasive cancer in a hospital-based case-control study in São Paulo, Brazil. The investigation included 453 controls and 4 groups of cases (CIN1, n = 140; CIN2, n = 126; CIN3, n = 231; invasive cancer, n =108) recruited from two major public clinics between 2003 and 2005. Increasing concentrations of serum lycopene were negatively associated with CIN1, CIN3 and cancer, with odds ratios (OR) (95% CI) for the highest compared to the lowest tertile of 0.53 (0.27-1.00, p for trend = 0.05), 0.48 (0.22-1.04, p for trend = 0.05) and 0.18 (0.06-0.52, p for trend = 0.002), respectively, after adjusting for confounding variables and HPV status. Increasing concentrations of serum alpha- and gamma-tocopherols, and higher dietary intakes of dark green and deep yellow vegetables/fruit were associated with nearly 50% decreased risk of CIN3. These results support the evidence that a healthy and balanced diet leading to provide high serum levels of antioxidants may reduce cervical neoplasia risk in low-income women.

TP53 and EGFR mutations in combination with lifestyle risk factors in tumours of the upper aerodigestive tract from South America.

Cancers of the upper aerodigestive tract [(UADT): oral cavity, pharynx, larynx and oesophagus] have high incidence rates in some parts of South America. Alterations in the TP53 gene are common in these cancers. In our study, we have estimated the prevalence and patterns of TP53 mutations (exons 4-10) in 236 UADT tumours from South America in relation to lifestyle risk factors, such as tobacco smoking and alcohol drinking. Moreover, we have conducted a pilot study of EGFR mutations (exons 18-21) in 45 tumours from the same population. TP53 mutation prevalence was high: 59% of tumours were found to carry mutant TP53. We found an association between TP53 mutations and tobacco smoking and alcohol drinking. The mutation rate increased from 38% in never-smokers to 66% in current smokers (P-value for trend = 0.09). G:C>T:A transversions were found only in smokers (15%). Alcohol drinkers carried more G:C>A:T transitions (P = 0.08). Non-exposed individuals were more probable to carry G:C>A:T transitions at CpG sites (P = 0.01 for never-smokers and P < 0.001 for never-drinkers). EGFR mutations were found in 4% of cases. Inactivation of TP53 by mutations is a crucial molecular event in the UADT carcinogenesis and it is closely related to exposure to lifestyle risk factors. EGFR mutations do not appear to be a common event in UADT carcinogenesis in this population.